- Novel benzoic thiazolidin-4-one derivatives targeting DevR/DosR dormancy regulator of Mycobacterium tuberculosis
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Latent tuberculosis infection is caused by Mycobacterium tuberculosis (Mtb) persistence and poses a significant challenge to the eradication of tuberculosis. The detection of Mtb DevR/DosR dormancy regulon expression in clinical specimens has provided evi
- Gupta, Rajesh Kumar,Jain, Neha,Kumar, Amit,Sarkar, Anjana,Sharma, Deeksha,Sharma, Saurabh,Sinha, Niharika,Tyagi, Jaya Sivaswami
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- New benzoxazole derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative evaluation, flowcytometric analysis, and in silico studies
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A new series of benzoxazole derivatives were designed and synthesised to have the main essential pharmacophoric features of VEGFR-2 inhibitors. Cytotoxic activities were evaluated for all derivatives against two human cancer cell lines, MCF-7 and HepG2. A
- Elkady, Hazem,Elwan, Alaa,El-Mahdy, Hesham A.,Doghish, Ahmed S.,Ismail, Ahmed,Taghour, Mohammed S.,Elkaeed, Eslam B.,Eissa, Ibrahim H.,Dahab, Mohammed A.,Mahdy, Hazem A.,Khalifa, Mohamed M.
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p. 397 - 410
(2021/12/31)
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- Discovery of new quinoxaline-based derivatives as anticancer agents and potent VEGFR-2 inhibitors: Design, synthesis, and in silico study
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VEGFR-2 is one of the most vital targets for the treatment of solid tumors. This work represents synthetic approaches of new set of quinoxaline-based derivatives having comparable essential pharmacophoric properties of VEGFR-2 inhibitors. The antiproliferative findings revealed that compound 21a displayed the most potent effect against MCF-7 and HepG2 cell lines with IC50 values of 12.9 and 7.5 μM, respectively. Further assessment was carried out for all the synthesized members against VEGFR-2 enzyme. Excitingly, the data of VEGFR-2 assay were comparable to that of antiproliferative assay. Compound 21a was the most powerful member against VEGFR-2 with an IC50 value of 3.8 nM, comparing to sorafenib (IC50 = 3.12 nM). Finally, molecular docking experiments were conducted to foresee how the synthesized compounds can bind to their prospective biological target; VEGFR-2. The docking results showed the ability of the synthesized compounds to bind VEGFR-2 in a correct manner. Lastly, computational physicochemical estimation of the most active candidates displayed that they have favorable assets with reasonable drug-likeness reports.
- Al-Hossaini, Abdulah M.,Alanazi, Mohammed M.,Alanazi, Wael A.,Alharbi, Madhawi A.,Alsaif, Nawaf A.,Dahab, Mohammed A.,Eissa, Ibrahim H.,Elkady, Hazem,Obaidullah, Ahmad J.
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- Targeting VEGFR-2 by new quinoxaline derivatives: Design, synthesis, antiproliferative assay, apoptosis induction, and in silico studies
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Twelve new triazolo[4,3-a]quinoxaline-based compounds are reported as anticancer agents with potential effects against vascular endothelial growth factor receptor-2 (VEGFR-2), using sorafenib as a reference molecule. With sorafenib as the positive control, the antiproliferative effects of the synthesized compounds against MCF-7 and HepG2 cells, as well as their VEGFR-2-inhibitory activities, were assessed. The most powerful VEGFR-2 inhibitor was compound 14a, which had an IC50 value of 3.2 nM, which is very close to that of sorafenib (IC50 = 3.12 nM). Furthermore, compounds 14c and 15d showed potential inhibitory activity against VEGFR-2, with IC50 values of 4.8 and 5.4 nM, respectively. Compound 14a caused apoptosis in HepG2 cells and stopped the cell cycle at the G2/M phase. In HepG2 cells, it also increased the levels of the proteases caspase-3 and caspase-9, as well as the Bax/Bcl-2 ratio. In silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) and toxicity experiments revealed that the synthesized agents had acceptable drug-likeness.
- Alsaif, Nawaf A.,Mahdy, Hazem A.,Alanazi, Mohammed M.,Obaidullah, Ahmad J.,Alkahtani, Hamad M.,Al-Hossaini, Abdullah M.,Al-Mehizi, Abdulrahman A.,Elwan, Alaa,Taghour, Mohammed S.
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- Design, synthesis, molecular docking, anticancer evaluations, and in silico pharmacokinetic studies of novel 5-[(4-chloro/2,4-dichloro)benzylidene]thiazolidine-2,4-dione derivatives as VEGFR-2 inhibitors
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The anticancer activity of novel thiazolidine-2,4-diones was evaluated against HepG2, HCT-116, and MCF-7 cells. MCF-7 was the most sensitive cell line to the cytotoxicity of the new derivatives. In particular, compounds 18, 12, 17, and 16 were found to be the most potent derivatives over all the tested compounds against the cancer cell lines HepG2, HCT116, and MCF-7, with IC50 = 9.16 ± 0.9, 8.98 ± 0.7, 5.49 ± 0.5 μM; 9.19 ± 0.5, 8.40 ± 0.7, 6.10 ± 0.4 μM; 10.78 ± 1.2, 8.87 ± 1.5, 7.08 ± 1.6 μM; and 10.87 ± 0.8, 9.05 ± 0.7, 7.32 ± 0.4 μM, respectively. Compounds 18 and 12 have nearly the same activities as sorafenib (IC50 = 9.18 ± 0.6, 5.47 ± 0.3, and 7.26 ± 0.3 μM, respectively), against HepG2 cells, but slightly lower activity against HCT116 cells and slightly higher activity against the MCF-7 cancer cell line. Also, these compounds displayed lower activities than doxorubicin against HepG2 and HCT-116 cells but higher activity against MCF-7 cells (IC50 = 7.94 ± 0.6, 8.07 ± 0.8, and 6.75 ± 0.4 μM, respectively). In contrast, compounds 17 and 16 exhibited lower activities than sorafenib against HepG2 and HCT116 cells, but nearly equipotent activity against the MCF-7 cancer cell line. Also, these compounds displayed lower activities than doxorubicin against the three cell lines. All the synthesized derivatives 7–18 were evaluated for their inhibitory activities against VEGFR-2. The tested compounds displayed high to medium inhibitory activity, with IC50 values ranging from 0.17 ± 0.02 to 0.27 ± 0.03 μM. Compounds 18, 12, 17, and 16 potently inhibited VEGFR-2 at IC50 values of 0.17 ± 0.02, 0.17 ± 0.02, 0.18 ± 0.02, and 0.18 ± 0.02 μM, respectively, which are nearly more than half of that of the IC50 value for sorafenib (0.10 ± 0.02 μM).
- El-Adl, Khaled,El-Helby, Abdel-Ghany A.,Sakr, Helmy,Ayyad, Rezk R.,Mahdy, Hazem A.,Nasser, Mohamed,Abulkhair, Hamada S.,El-Hddad, Sanadelaslam S. A.
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- Design, synthesis, and anti-proliferative evaluation of new quinazolin-4(3H)-ones as potential VEGFR-2 inhibitors
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Inhibiting VEGFR-2 has been set up as a therapeutic strategy for treatment of cancer. Thus, nineteen new quinazoline-4(3H)-one derivatives were designed and synthesized. Preliminary cytotoxicity studies of the synthesized compounds were evaluated against three human cancer cell lines (HepG-2, MCF-7 and HCT-116) using MTT assay method. Doxorubicin and sorafenib were used as positive controls. Five compounds were found to have promising cytotoxic activities against all cell lines. Compound 16f, containing a 2-chloro-5-nitrophenyl group, has emerged as the most active member. It was approximately 4.39-, 5.73- and 1.96-fold more active than doxorubicin and 3.88-, 5.59- and 1.84-fold more active than sorafenib against HepG2, HCT-116 and MCF-7 cells, respectively. The most active cytotoxic agents were further evaluated in vitro for their VEGFR-2 inhibitory activities. The results of in vitro VEGFR-2 inhibition were consistent with that of the cytotoxicity data. Molecular docking of these compounds into the kinase domain, moreover, supported the results.
- El-Adl, Khaled,El-Helby, Abdel-Ghany A.,Ayyad, Rezk R.,Mahdy, Hazem A.,Khalifa, Mohamed M.,Elnagar, Hamdy A.,Mehany, Ahmed B.M.,Metwaly, Ahmed M.,Elhendawy, Mostafa A.,Radwan, Mohamed M.,ElSohly, Mahmoud A.,Eissa, Ibrahim H.
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- Design, synthesis and biological evaluation of novel 5-(4-chlorophenyl)-4-phenyl-4H-1,2,4-triazole-3-thiols as an anticancer agent
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Cellular tumor antigen p53 is significant for cancer prevention and its mutation is most documented genomic change in human cancers. Thus, restoration of p53 function by interruption of the p53-MDM2 interaction opens up a prospect for a nongenotoxic anticancer therapeutic strategy. A novel series of molecules comprising 1,2,4-triazole-3-thiol scaffold were successfully discovered by structure-based designing approach. In silico modules predicted that 5-(4-chlorophenyl)-4-phenyl-4H-1,2,4-triazole-3-thiol derivatives have draggability and ability to mimic critical binding residues of p53. All target compounds were assayed for their in vitro antiproliferative activity against A549, U87 and HL60 cell lines. Twelve out of sixteen compounds exhibited good in vitro inhibitory activity in micromolar range. Especially, compound 6h possessed acute antitumor activity with IC50 values 3.854, 4.151 and 17.522 μM against three tested cell lines. It represents as a promising lead for further optimization and a template for development of novel antitumor agents.
- Patel, Krupa R.,Brahmbhatt, Jpan G.,Pandya, Pranav A.,Daraji, Drashti G.,Patel, Hitesh D.,Rawal, Rakesh M.,Baran, Sujit K.
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- New quinoxaline derivatives as VEGFR-2 inhibitors with anticancer and apoptotic activity: Design, molecular modeling, and synthesis
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New series of [1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-one and [1,2,4]triazolo[4,3-a]quinoxaline derivatives have been designed, synthesized, and biologically assessed for their anti-proliferative activities against two selected tumor cell lines MCF-7 and HepG2. Comparing to sorafenib (IC50 = 2.17 ± 0.13 and 3.51 ± 0.21 μM against MCF-7 and HepG2, respectively), compound 25d, 25e, 25i, and 27e exhibited the highest activities against the examined cell lines with IC50 values extending from 4.1 ± 0.4 to 11.7 ± 1.1 μM. Furthermore, VEGFR-2 inhibitory activities were assessed for all the synthesized compounds as potential mechanisms for their anti-proliferative activities. Compounds 25d, 25e, 25i, and 27e displayed prominent inhibitory efficiency versus VEGFR-2 kinase with IC50 value ranging from 3.4 ± 0.3 to 6.8 ± 0.5 nM. Fascinatingly, the results of VEGFR-2 inhibitory assays were matched with that of the cytotoxicity data, where the most potent anti-proliferative derivatives exhibited promising VEGFR-2 inhibitory activities. Further studies displayed the ability of compound 25d to induce apoptosis in HepG2 cells and can arrest the growth of such cells at the G2/M phase. Also, compound 25d produced a significant increase in the level of BAX/Bcl-2 ratio (3.8-fold), caspase- 3 (1.8-fold), and caspase-9 (1.9-fold) compared to the control cells. Molecular docking studies were carried out to investigate the possible binding interaction inside the active site of the VEGFR-2.
- Alsaif, Nawaf A.,Dahab, Mohammed A.,Alanazi, Mohammed M.,Obaidullah, Ahmad J.,Al-Mehizia, Abdulrahman A.,Alanazi, Manal M.,Aldawas, Saleh,Mahdy, Hazem A.,Elkady, Hazem
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- Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives as anticancer agents and apoptosis inducers
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Herein, a new wave of bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives have been successfully designed and synthesised. The synthesised derivatives were biologically investigated for their cytotoxic activities against HepG2 and MCF-7. Also, the tested compounds were further examined in?vitro for their VEGFR-2 inhibitory activity. The most promising derivative 23j was further investigated for its apoptotic behaviour in HepG2 cell lines using flow cytometric and western-plot analyses. Additional in-silico studies were performed to predict how the synthesised compounds can bind to VEGFR-2 and to determine the drug-likeness profiling of these derivatives. The results revealed that compounds 23a, 23i, 23j, 23l, and 23n displayed the highest antiproliferative activities against the two cell lines with IC50 values ranging from 6.4 to 19.4 μM. Furthermore, compounds 23a, 23d, 23h, 23i, 23j, 23l, 23 m, and 23n showed the highest VEGFR-2 inhibitory activities with IC50 values ranging from 3.7 to 11.8 nM, comparing to sorafenib (IC50 = 3.12 nM). Moreover, compound 23j arrested the HepG2 cell growth at the G2/M phase and induced apoptosis by 40.12% compared to the control cells (7.07%). As well, such compound showed a significant increase in the level of caspase-3 (1.36-fold), caspase-9 (2.80-fold), and BAX (1.65-fold), and exhibited a significant decrease in Bcl-2 level (2.63-fold).
- Alsaif, Nawaf A.,Taghour, Mohammed S.,Alanazi, Mohammed M.,Obaidullah, Ahmad J.,Al-Mehizia, Abdulrahman A.,Alanazi, Manal M.,Aldawas, Saleh,Elwan, Alaa,Elkady, Hazem
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p. 1093 - 1114
(2021/06/11)
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- New quinoxaline-based VEGFR-2 inhibitors: Design, synthesis, and antiproliferative evaluation with: In silico docking, ADMET, toxicity, and DFT studies
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A new series of 3-methylquinoxaline-based derivatives having the same essential pharmacophoric features as VEGFR-2 inhibitors have been synthesized and evaluated for their antiproliferative activities against two human cancer cell lines, MCF-7 and HepG-2. Compounds 15b and 17b demonstrated a significant antiproliferative effect with IC50 ranging from 2.3 to 5.8 μM. An enzymatic assay was carried out for all the tested candidates against VEGFR-2. Compound 17b was the most potent VEGFR-2 inhibitor (IC50 = 2.7 nM). Mechanistic investigation including cell cycle arrest and apoptosis was performed for compound 17b against HepG-2 cells, and the results revealed that 17b induced cell apoptosis and arrested cell cycle in the G2/M phase. Moreover, apoptosis analyses were conducted for compound 17b to evaluate its apoptotic potential. The results showed upregulation in caspase-3 and caspase-9 levels, and improving the Bax/Bcl-2 ratio by more than 10-fold. Docking studies were performed to determine the possible interaction with the VEGFR-2 active site. Further docking studies were carried out for compound 17b against cytochrome P450 to present such compounds as non-inhibitors. In silico ADMET, toxicity, and physico-chemical properties revealed that most of the synthesized members have acceptable values of drug-likeness. Finally, DFT studies were carried out to calculate the thermodynamic, molecular orbital and electrostatic potential properties.
- Alanazi, Manal M.,Alanazi, Mohammed M.,Alharbi, Madhawi A.,Alkahtani, Hamad M.,Alsaif, Nawaf A.,Dahab, Mohammed A.,Eissa, Ibrahim H.,Elkady, Hazem,Obaidullah, Ahmad J.
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p. 30315 - 30328
(2021/10/25)
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- Synthesis, Molecular Docking and Biological Evaluation of 2-Aryloxy-N-Phenylacetamide and N′-(2-Aryloxyoxyacetyl) Benzohydrazide Derivatives as Potential Antibacterial Agents
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A new class of 2-aryloxy-N-phenylacetamide and N′-(2-aryloxyoxyacetyl) benzohydrazide derivatives with different active moieties were synthesized and screened for their antibacterial activity. Structural characterization of synthesized compounds was perfo
- Yele, Vidyasrilekha,Azam, Mohammad Afzal,Wadhwani, Ashish D.
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- New bis([1,2,4]triazolo)[4,3-a:3′,4′-c]quinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers: Design, synthesis, in silico studies, and anticancer evaluation
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A new series of bis([1,2,4]triazolo)[4,3-a:3′,4′-c]quinoxaline derivatives were designed and synthesized to have the main essential pharmacophoric features of VEGFR-2 inhibitors. VEGFR-2 inhibitory activities were assessed for the designed compounds. In addition, cytotoxic activity was evaluated for all derivatives against two human cancer cell lines namely, HepG-2 and MCF-7. The most cytotoxic compound 20 h was subjected to further biological investigations including cell cycle, apoptosis, caspase-3, caspase-9, BAX, and Bcl-2 analyses. Different in silico studies as docking, ADMET and toxicity were carried out. The results exhibited that compounds 20b, 20e, 20h and 20m showed promising VEGFR-2 inhibitory activities with IC50 values of 5.7, 6.7, 3.2, and 3.1 μM, respectively. Moreover, these promising members exhibited the highest antiproliferative activities against the two cell lines with IC50 values ranging from 3.3 to 14.2 μM, comparing to sorafenib (IC50 = 2.17 and 3.43 μM against HepG2 and MCF-7, respectively). Additionally, compound 20h induced cell cycle arrest of HepG2 cells at G2/M phase. Also, such compound increased the progress of apoptosis by 3.5-fold compared to the control. As well, compound 20h showed a significant increase in the level of caspase-3 (2.07-fold), caspase-9 (1.72-fold), and BAX (1.83-fold), and a significant decrease in Bcl-2 level (1.92-fold). The in silico studies revealed that the synthesized compounds have binding pattern like that of sorafenib.
- Alanazi, Mohammed M.,Mahdy, Hazem A.,Alsaif, Nawaf A.,Obaidullah, Ahmad J.,Alkahtani, Hamad M.,Al-Mehizia, Abdulrahman A.,Alsubaie, Sultan M.,Dahab, Mohammed A.,Eissa, Ibrahim H.
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- Discovery of new quinoxaline-2(1H)-one-based anticancer agents targeting VEGFR-2 as inhibitors: Design, synthesis, and anti-proliferative evaluation
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VEGF/VEGFR2 pathway is the crucial therapeutic target in the treatment of cancer. So that, a new series of quinoxaline-2(1H)-one derivatives were designed and synthesized. The synthesized compounds were tested against three human cancer cell lines (HepG-2, MCF-7 and HCT-116) aiming to evaluate its anti-proliferative activities. Doxorubicin as a universal anticancer drug and sorafenib as a potent VEGFR-2 inhibitor were used as positive controls. The data obtained from biological activity were found highly correlated with that obtained from molecular modeling studies. The most sensitive cell line to the influence of our new derivatives was HCT-116. Compounds 13b, 15, 16e and 17b exert the highest cytotoxic activities against the tested cell lines. Overall, compound 15 was the most active member with IC50 values of 5.30, 2.20, 5.50 μM against HepG-2, MCF-7 and HCT-116, respectively. Compounds 15 and 17b showed better anti-proliferative activities than doxorubicin and sorafenib against the three cancer cell lines. Additionally, compound 16e showed better anti-proliferative activities than doxorubicin and sorafenib against HepG-2 and HCT-116 but exhibited lower activity against MCF-7 cell line. In addition, the most promising members were further evaluated for their inhibitory activities against VEGFR-2. Compounds 15 and 17b potently inhibited VEGFR-2 at lower IC50 values of 1.09 and 1.19 μM, respectively, compared to sorafenib (IC50 = 1.27 μM). Moreover, docking studies were conducted to investigate the binding pattern of the synthesized compounds against the prospective molecular target VEGFR-2.
- El-Adl, Khaled,Sakr, Helmy M.,Yousef, Reda G.,Mehany, Ahmed B.M.,Metwaly, Ahmed M.,Elhendawy, Mostafa A.,Radwan, Mohamed M.,ElSohly, Mahmoud A.,Abulkhair, Hamada S.,Eissa, Ibrahim H.
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- Identification of new [1,2,4]triazolo[4,3-a]quinoxalines as potent VEGFR-2 tyrosine kinase inhibitors: Design, synthesis, anticancer evaluation, and in silico studies
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Tumor angiogenesis is mainly regulated by VEGFR-2. In this study, a new series of [1,2,4]triazolo[4,3-a]quinoxaline based-derivatives has been designed and synthesized to develop new anti-proliferative and anti-VEGFR-2 members. Anti-proliferative activities of the synthesized compounds were tested against MCF-7 and HepG2 cell lines. Compound 19a exhibited the highest activity towards both MCF-7 and HepG2 cell lines (IC50 = 8.2 and 5.4 μM, respectively), compared to sorafenib (IC50 = 3.51 and 2.17 μM, respectively). Additionally, all compounds were screened to evaluate their effect as VEGFR-2 inhibitors. Compound 19a (IC50 = 3.4 nM) exhibited good activity compared to sorafenib (IC50 = 3.12 nM). Furthermore, compound 19a disrupted the HepG2 cell cycle by arresting the G2/M phase. Also, marked increase in the percentage apoptotic cells was achieved by compound 19a. The induced apoptotic effect of compound 19a in HepG2 cells was assured by increased pro‐apoptotic marker (Bax) expression by 2.33-fold and decreased anti‐apoptotic (Bcl‐2) expression by 1.88-fold, resulting in an elevation of the Bax/Bcl-2 ratio in HepG2 cells. Comparing to the control cells, compound 19a induced an increase in expression of cleaved caspase-3 and caspase-9 by 2.44- and 2.69-fold, respectively. Finally, the binding modes of the target derivatives were investigated through docking studies against the proposed molecular target (VEGFR-2, PDB ID: 2OH4).
- Alsaif, Nawaf A.,Taghour, Mohammed S.,Alanazi, Mohammed M.,Obaidullah, Ahmad J.,Alanazi, Wael A.,Alasmari, Abdullah,Albassam, Hussam,Dahab, Mohammed A.,Mahdy, Hazem A.
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- Design, synthesis, kinetic, molecular dynamics, and hypoglycemic effect characterization of new and potential selective benzimidazole derivatives as Protein Tyrosine Phosphatase 1B inhibitors
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Protein-tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling pathway and has been validated as a therapeutic target for type 2 diabetes. A wide variety of scaffolds have been included in the structure of PTP1B inhibitors, one of them is the benzimidazole nucleus. Here, we report the design and synthesis of a new series of di- and tri- substituted benzimidazole derivatives including their kinetic and structural characterization as PTP1B inhibitors and hypoglycemic activity. Results show that compounds 43, 44, 45, and 46 are complete mixed type inhibitors with a Ki of 12.6 μM for the most potent (46). SAR type analysis indicates that a chloro substituent at position 6(5), a β-naphthyloxy at position 5(6), and a p-benzoic acid attached to the linker 2-thioacetamido at position 2 of the benzimidazole nucleus, was the best combination for PTP1B inhibition and hypoglycemic activity. In addition, molecular dynamics studies suggest that these compounds could be potential selective inhibitors from other PTPs such as its closest homologous TCPTP, SHP-1, SHP-2 and CDC25B. Therefore, the compounds reported here are good hits that provide structural, kinetic, and biological information that can be used to develop novel and selective PTP1B inhibitors based on benzimidazole scaffold.
- Campos-Almazán, Mara Ibeth,Flores-Ramos, Miguel,Hernández-Campos, Alicia,Castillo, Rafael,Sierra-Campos, Erick,Torgeson, Kristiane,Peti, Wolfgang,Valdez-Solana, Mónica,Oria-Hernández, Jesús,Méndez, Sara T.,Castillo-Villanueva, Adriana,Jiménez-de Jesús, Hugo,Avitia-Domínguez, Claudia,Téllez-Valencia, Alfredo
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- Design, synthesis and molecular docking of new [1,2,4] triazolo[4,3-a]quinoxaline derivatives as anticancer agents targeting VEGFR-2 kinase
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Abstract: Vascular endothelial growth factor receptor-2 (VEGFR-2) is critically involved in cancer angiogenesis. Blocking of VEGFR-2 signaling pathway proved effective suppression of tumor growth. Accordingly, two series of new triazoloquinoxaline-based derivatives were designed and synthesized as VEGFR-2 inhibitors. All in vitro cytotoxic activities of the synthesized compounds were evaluated against two human cancer cell lines (MCF-7 and HepG2). To confirm the potential mechanism of cytotoxicity, enzymatic assays against VEGFR-2 were estimated for all the target compounds. The results of VEGFR-2 inhibitory activity and cytotoxicity were in high correlation. Compound 22a exhibited the highest cytotoxic effect with IC50 values of 6.2 and 4.9?μM against MCF-7 and HepG2, respectively, comparing to sorafenib (IC50 = 3.53 and 2.18?μM). Such derivative showed the best VEGFR-2 inhibitory activity with an IC50 value of 3.9?nM, which is very close to that of sorafenib (IC50 = 3.13?nM). Moreover, compounds 22b, 23b, and 23e exhibited strong cytotoxic activity with IC50 values ranging from 11.7 to 15.3?μM. Also, these compounds showed promising VEGFR-2 inhibition with IC50 values of 4.2, 5.7, and 4.7?nM, respectively. In silico docking, ADMET, and toxicity studies were carried out for the synthesized compounds. The results revealed that some compounds have a good binding mode against VEGFR-2 and a high level of drug-likeness. Graphic abstract: [Figure not available: see fulltext.]
- Alanazi, Mohammed M.,Alanazi, Wael A.,Alasmari, Abdullah F.,Albassam, Hussam,Alsaif, Nawaf A.,Elwan, Alaa,Mahdy, Hazem A.,Obaidullah, Ahmad J.,Taghour, Mohammed S.
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- New Mercaptoacetamide Derivatives: Synthesis and Assessment as Antimicrobial and Antimycobacterial Agents
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During last few years, the frightening elevation of bacterial resistance was accompanied by dramatic decline in recent treatments of infectious diseases, which became a point of anxiety for healthcare industries. MDR and XDR strains of Mycobacterium tuberculosis (Mtb) result in the tuberculosis. In this regard, herein, a series of new mercaptoacetamide derivatives were synthesized via multipot synthetic pathway and the rationale was the appraisal of bioactivity in compact heteronuclei and their assessment as potential antimicrobial and antimycobacterial agents against virulent strain of Mtb, H37Ra for structure–activity relationship (SAR) studies. The inhibition zones of compounds 4c and 4e were found to be nearest to that of standard drug Ciprofloxacin, while compounds 4h and 4j were mild to moderately active against Gram positive bacteria (Staphylococcus aureus, Streptococus pneumonia) and Gram negative bacteria (Pseudomonas aeruginosa, Salmonella typhimurium and Escherichia coli). MIC90 assays indicated that new mercaptoacetamides did not exhibit in vitro activity against Mtb in contrast to Rifampicin and Streptomycin, first-line antimycobacterial chemotherapeutic agents. According to the present study, it was concluded that mercaptoacetamides of the new series succeeded as antimicrobial agents but could not develop as potential lead compounds against Mtb when tested in concentrations of 50, 25, 12.5 and 6.25 μg/mL.
- Hashim, Syed Riaz,Hegde, Rahul Rama,Pal, Dilipkumar,Rani, Priyanka
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p. 715 - 723
(2021/10/27)
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- Design, synthesis, molecular modeling, in vivo studies and anticancer activity evaluation of new phthalazine derivatives as potential DNA intercalators and topoisomerase II inhibitors
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Herein we report the design and synthesis of a new series of phthalazine derivatives as Topo II inhibitors and DNA intercalators. The synthesized compounds were in vitro evaluated for their cytotoxic activities against HepG-2, MCF-7 and HCT-116 cell lines. Additionally, Topo II inhibitory activity and DNA intercalating affinity were investigated for the most active compounds as a potential mechanism for the anticancer activity. Compounds 15h, 23c, 32a, 32b, and 33 exhibited the highest activities against Topo II with IC50 ranging from 5.44 to 8.90 μM, while compounds 27 and 32a were found to be the most potent DNA binders at IC50 values of 36.02 and 48.30 μM, respectively. Moreover, compound 32a induced apoptosis in HepG-2 cells and arrested the cell cycle at the G2/M phase. Besides, compound 32a showed Topo II poisoning effect at concentrations of 2.5 and 5 μM, and Topo II catalytic inhibitory effect at a concentration of10 μM. In addition, compound 32b showed in vivo a significant tumor growth inhibition effect. Furthermore, molecular docking studies were carried out against DNA-Topo II complex and DNA to investigate the binding patterns of the designed compounds.
- Khalifa, mohamed m.,Radwan, mohamed m.,Rashed, mahmoud,Sakr, Helmy,ayyad, Rezk R.,belal, amany,eissa, Ibrahim H.,el-Helby, abdel-Ghany a.,el-Sharkawy, abdou,elSohly, mahmoud a.,elhendawy, mostafa a.,mahdy, Hazem a.,metwaly, ahmed m.
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- Discovery of new quinazolin-4(3H)-ones as VEGFR-2 inhibitors: Design, synthesis, and anti-proliferative evaluation
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Sixteen novel quinazoline-based derivatives were designed and synthesized via modification of the VEGFR-2 reported inhibitor 7 in order to increase the binding affinity of the designed compounds to the receptor active site. The designed compounds were evaluated for their VEGFR-2 inhibitory effects. Inhibiting VEGFR-2 has been set up as a therapeutic strategy for treatment of cancer. The bioactivity of the new compounds was performed against HepG-2, MCF-7 and HCT-116 cell lines. Doxorubicin and sorafenib were used as positive controls. Compound 18d was observed to have promising cytotoxic activity (IC50 = 3.74 ± 0.14, 5.00 ± 0.20 and 6.77 ± 0.27 μM) in comparison to the reference drug doxorubicin (IC50 = 8.28, 9.63 and 7.67 μM) and sorafenib (IC50 = 7.31, 9.40 and 7.21 μM). The most active compounds were tested for their in vitro VEGFR-2 inhibitory activities. Results of VEGFR-2 inhibition were consistent with that of the cytotoxicity data. Thus, compound 18d showed VEGFR-2 inhibitory activity (IC50 = 0.340 ± 0.04 μM) superior to that of the reference drug, sorafenib (IC50 = 0.588 ± 0.06 μM). Furthermore, docking study was performed in order to understand the binding pattern of the new compounds into VEGFR-2 active site. Docking results attributed the potent VEGFR-2 inhibitory effect of the new compounds as they bound to the key amino acids in the active site, Glu883 and Asp1044, as well as their hydrophobic interaction with the receptor hydrophobic pocket. Results of cytotoxic activities, in vitro VEGFR-2 inhibition together with docking study argument the advantages of the synthesized analogues as promising anti-angiogenic agents.
- Eissa, Ibrahim H.,El-Helby, Abdel-Ghany A.,Mahdy, Hazem A.,Khalifa, Mohamed M.,Elnagar, Hamdy A.,Mehany, Ahmed B.M.,Metwaly, Ahmed M.,Elhendawy, Mostafa A.,Radwan, Mohamed M.,ElSohly, Mahmoud A.,El-Adl, Khaled
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- Utilization of tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinone as a cap moiety in design of novel histone deacetylase inhibitors
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A series of novel 5,6,7,8-Tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one derivatives bearing a hydroxamic acid, 2-aminoanilide and hydrazide moieties as zinc-binding group (ZBG) were designed, synthesized and evaluated for the HDAC inhibition activity
- Mohamed, Mamdouh F.A.,Youssif, Bahaa G.M.,Shaykoon, Montaser Sh. A.,Abdelrahman, Mostafa H.,Elsadek, Bakheet E.M.,Aboraia, Ahmed S.,Abuo-Rahma, Gamal El-Din A.
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- Pharmacological and physicochemical profile of arylacetamides as tools against human cancers
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Arylacetamides are widely used as synthetic intermediates to obtain medicinal substances. This work evaluated in vitro antiproliferative activity of ten 2-Chloro-N-arylacetamides on human normal and cancer cells and detailed in vivo toxicological and anticancer investigations. Initially, cytotoxic colorimetric assays were performed using tumor lines, peripheral blood mononuclear cells (PBMC) and erythrocytes. Compounds 2, 3 and 4 were tested for acute toxicity (50, 150 and 300 mg/kg) and for subacute antitumoral capacity in HCT-116 colon carcinoma-bearing xenograft mice for 15 days at 25 mg/kg/day. Most compounds revealed cytotoxic action on tumor lines and PBMC, but activity on human erythrocytes were not detected. Molecular dipole moment, lipophilicity and electronic constant of aryl substituents had effects upon in vitro antiproliferative capacity. More common in vivo acute behavioral signals with compounds 2, 3 and 4 were muscle relaxation, reduction of spontaneous locomotor activity and number of entries in closed arms and increased number of falls andtime spent in open arms, suggesting diazepam-like anxiolytic properties. Decrease of grabbing strength and overall activity were common, but palpebral ptosis and deaths occurred at 300 mg/kg only. Compounds 2 and 3 reduced colon carcinoma growth (21.2 and 27.5%, respectively, p 0.05) without causing apparent signals of organ-specific toxicity after subacute exposure. The structural chemical simplicity of arylacetamides make them cost-effective alternatives and justifies further improvements to enhance activity, selectivity and the development of pharmaceutical formulations.
- Ferreira, Paulo Michel Pinheiro,Machado, Kátia da Concei??o,Lavorato, Stefania Neiva,de Oliveira, Fátima de Cássia Evangelista,Silva, Jurandy do Nascimento,de Almeida, Antonia Amanda Cardoso,Santos, Luciano de Souza,Silva, Valdenizia Rodrigues,Bezerra, Daniel Pereira,Soares, Milena Botelho Pereira,Pessoa, Cláudia,de Moraes Filho, Manoel Odorico,Ferreira, José Roberto de Oliveira,Sousa, Jo?o Marcelo de Castro e,Maltarollo, Vinícius Gon?alves,Alves, Ricardo José
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- Symmetric molecules with 1,4-triazole moieties as potent inhibitors of tumour-associated lactate dehydrogenase-A
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A series of symmetric molecules incorporating aryl or pyridyl moieties as central core and 1,4-substituted triazoles as a side bridge was synthesised. The new compounds were investigated as lactate dehydro-genase (LDH, EC 1.1.1.27) inhibitors. The cancer associated LDHA isoform was inhibited with IC50 = 117–174?μM. Seven compounds exhibited better LDHA inhibition (IC50 117–136?μM) compared to known LDH inhibitor–galloflavin (IC50 157?μM).
- Altamimi, Abdul-Malek S.,Abdel-Gawad, Sherif A.,Alafeefy, Ahmed M.,Balode, Agnese,Vozny, Igor,Pustenko, Aleksandrs,?alubovskis, Raivis,El Shikh, Mohey Eldin,Alasmary, Fatmah A. S.
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p. 147 - 150
(2018/01/02)
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- Structural optimization of N1-aryl-benzimidazoles for the discovery of new non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains
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Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are recommended components of preferred combination antiretroviral therapies used for the treatment of human immunodeficiency virus (HIV) infection. These regimens are extremely effective in suppressing virus replication. Recently, our research group identified some N1-aryl-2-arylthioacetamido-benzimidazoles as a novel class of NNRTIs. In this research work we report the design, the synthesis and the structure–activity relationship studies of new compounds (20–34) in which some structural modifications have been introduced in order to investigate their effects on reverse transcriptase (RT) inhibition and to better define the features needed to increase the antiviral activity. Most of the new compounds proved to be highly effective in inhibiting both RT enzyme at nanomolar concentrations and HIV-1 replication in MT4 cells with minimal cytotoxicity. Among them, the most promising N1-aryl-2-arylthioacetamido-benzimidazoles and N1-aryl-2-aryloxyacetamido-benzimidazoles were also tested toward a panel of single- and double-mutants strain responsible for resistance to NNRTIs, showing in vitro antiviral activity toward single mutants L100I, K103N, Y181C, Y188L and E138K. The best results were observed for derivatives 29 and 33 active also against the double mutants F227L and V106A. Computational approaches were applied in order to rationalize the potency of the new synthesized inhibitors.
- Monforte, Anna Maria,De Luca, Laura,Buemi, Maria Rosa,Agharbaoui, Fatima E.,Pannecouque, Christophe,Ferro, Stefania
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p. 661 - 674
(2018/01/03)
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- Carbamylmethyl Mercaptoacetate Thioether: A Novel Scaffold for the Development of L1 Metallo-β-lactamase Inhibitors
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Given the clinical importance of metallo-β-lactamases (MβLs), a new scaffold, N-substituted carbamylmethyl mercaptoacetate thioether, was constructed. The obtained molecules 1-16 inhibited MβLs from all three subclasses, but preferentially L1 from subclass B3. Compound 9 with a p-carboxyphenyl substituent exhibited the broadest spectrum with at least 70% inhibition of enzymes from all subclasses at 100 μM, while compound 5 with a p-methylphenyl substituent was the most potent inhibitor of any individual enzyme, with 97% inhibition at 100 μM and an IC50 value of 0.41 μM against L1. Isothermal titration calorimetry assays corroborate findings from UV-vis spectrophotometric assays that the inhibition of L1 by 5 is dose-dependent. Docking studies suggest that the carboxyl group, the sulfide atom, and the carbonyl group of the carbamyl coordinate Zn2 in a chelating fashion. Using E. coli cells expressing L1, 6 and 8 were able to decrease cefazolin minimum inhibitory concentration 8-fold.
- Chang, Ya-Nan,Xiang, Yang,Zhang, Yue-Juan,Wang, Wen-Ming,Chen, Cheng,Oelschlaeger, Peter,Yang, Ke-Wu
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supporting information
p. 527 - 532
(2017/05/19)
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- Facile synthesis of some condensed 1,3-thiazines and thiazoles under conventional conditions: antitumor activity
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1,3-Thiazine 3 was obtained from cinnamoyl thiourea derivative 2 as the kinetic control product. Refluxing of 2 with sodium ethoxide afforded pyrimidine derivative 4. Moreover, stirring of 2 with bromine/acetic acid gave thiazole 5 that was condensed with o-phenylene diamine forming benzimidazole 6. Heating of arylthiourea 8 with maleic anhydride or phenacyl chloride afforded thiazole derivatives 9 and 10, respectively. Condensation of compound 10 with o-phenylene diamine gave benzimidazole 11. Reaction of p-amino benzoic acid with chloro acetyl isothiocyanate, acetylacetone and ethylacetoacetate produced imidazole 14, enaminone 15 and crotonate 16 derivatives, respectively. Stirring a mixture of benzoyl isothiocyanate with 15 and/or 16 resulted in pyridine-2-thione 17. The yields of the prepared compounds were 41–93%. The experimental section is simple and easy. The detailed synthesis, spectroscopic data, IC50 and antitumor activity of the synthesized compounds were reported. The cytotoxicity of the newly synthesized products showed that compound 4 is the most active compound towards the cancer cell line at which its reactivity is higher than that of the standard doxorubicin (anticancer reference drug).
- Haggam, Reda A.,Assy, Mohamed G.,Sherif, Mohamed H.,Galahom, Mohamed M.
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p. 6299 - 6315
(2017/10/05)
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- Development of novel Asf1-H3/H4 inhibitors
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The histone chaperone anti-silencing function 1 (Asf1) has emerged as a promising target for therapeutic intervention for multiple cancers (Cell 2006, 127, 458). Asf1 is involved in the packaging of the eukaryotic genome into chromatin, which is essential
- Miknis, Greg F.,Stevens, Sarah J.,Smith, Luke E.,Ostrov, David A.,Churchill, Mair E.A.
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supporting information
p. 963 - 968
(2015/02/19)
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- Synthesis and in vitro kinetic study of novel mono-pyridinium oximes as reactivators of organophosphorus (OP) inhibited human acetylcholinesterase (hAChE)
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A series of mono pyridinium oximes linked with arenylacetamides as side chains were synthesized and their in vitro reactivation potential was evaluated against human acetylcholinesterase (hAChE) inhibited by organophosphorus inhibitors (OP) such as sarin, VX and tabun. The reactivation data of the synthesized compounds were compared with those obtained with standard reactivators such as 2-PAM and obidoxime. The dissociation constant (KD) and specific reactivity (kr) of the oximes were also determined by performing reactivation kinetics against OP inhibited hAChE. Among the synthesized compounds, oximes 1-(2-(4-cyanophenylamino)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium chloride (12a) and 4-((hydroxyimino)methyl)-1-(2-(4-methoxyphenylamino)-2-oxoethyl)pyridinium chloride (2a) were found most potent reactivators for hAChE inhibited by sarin. In case of VX inhibited hAChE majority of the oximes have shown good reactivation efficacies. Among these oximes 1-(2-(benzylamino)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium chloride (18a), 4-((hydroxyimino)methyl)-1-(2-(4-(methoxycarbonyl)phenylamino)-2-oxoethyl)pyridinium-chloride (14a) and 12a were found to surpass the reactivation potential of 2-PAM and obidoxime. However, the synthesized oximes showed marginal reactivation efficacies in case of tabun inhibited hAChE. The pKa value of the oximes were determined and correlated with their observed reactivation potential.
- Valiveti, Aditya Kapil,Bhalerao, Uma M.,Acharya, Jyotiranjan,Karade, Hitendra N.,Gundapu, Raviraju,Halve, Anand K.,Kaushik, Mahabir Parshad
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p. 125 - 132
(2015/06/25)
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- Design, synthesis and glucose uptake activity of some novel glitazones
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Herein, we report a library consisting of some novel glitazones containing thiazolidinedione and its bioisosteres, rhodanine and oxadiazolidine ring structures as their basic scaffold for their antidiabetic activity. Twelve novel glitazones with diverse chemical structures were designed and synthesized by adopting appropriate synthetic schemes and analyzed. Later, subjected to in vitro glucose uptake assay in the absence and presence of insulin to confirm their antidiabetic activity using rat hemi-diaphragm. The titled compounds exhibited glucose uptake activity ranging weak to significant activity. Compounds 4, 5, 9, 11, 15, 16, 19 and 20 showed considerable glucose uptake activity apart from rosiglitazone, a standard drug. Compound 16 happens to be the candidate compound from this study to investigate further. The illustration about their design, synthesis, analysis and glucose uptake activity is reported here along with the in vitro and in silico study based structure-activity relationships.
- Kar, Koyel,Krithika, Uma,Mithuna,Basu, Prabhuddha,Santhosh Kumar,Reji, Anu,Prashantha Kumar
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- Gd3+ complexes conjugated to Pittsburgh compound B: Potential MRI markers of β-amyloid plaques Topical Issue on Metal-Based MRI Contrast Agents. Guest editor: Valerie C. Pierre
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In an effort towards the visualization of β-amyloid (Aβ) plaques by T 1-weighted magnetic resonance imaging for detection of Alzheimer's disease, we report the synthesis and characterization of stable, noncharged Gd3+ complexes of th
- Martins, André F.,Morfin, Jean-Fran?ois,Geraldes, Carlos F. G. C.,Tóth, éva
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p. 281 - 295
(2014/03/21)
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- Synthesis, cytotoxic study and docking based multidrug resistance modulator potential analysis of 2-(9-oxoacridin-10(9H)-yl)-N-phenyl acetamides
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The present study describes the synthesis of fifteen 2-(9-oxoacridin-10(9H) -yl)-N-phenyl acetamide derivatives (13a-o) through condensation of 2-chloro-N-phenyl acetamides (12a-o) with acridone molecule (10). All the synthesized compounds were screened f
- Kumar, Rajesh,Kaur, Maninder,Bahia, Malkeet Singh,Silakari, Om
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- Molecular modeling and synthesis of ZINC02765569 derivatives as protein tyrosine phosphatase 1B inhibitors: Lead optimization study
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This article describes design, synthesis, and molecular modeling studies of the ZINC02765569 derivatives as potent protein tyrosine phosphatase 1B (PTP1B) inhibitors, which was previously reported as a vHTS hit (ZINC02765569) by our laboratory. Ten compou
- Joshi, Prashant,Deora, Girdhar Singh,Rathore, Vandana,Rawat, Arun K.,Srivastava,Jain, Deepti
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p. 1618 - 1623
(2013/07/26)
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- Synthesis of novel 2-iminothiazolidin-4-ones
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Thiazolidin-4-ones are known to exhibit diverse biological activities such as antimicrobial, anticancer, antidiarrheal, anticonvulsant, antidiabetic, antihistaminic, and antifungal activities. In the present investigation, a series of 2-haloacetamides was prepared by reacting chloroacetyl chloride with amines in dry benzene under reflux conditions. The formed 2-haloacetamides reacted with potassium thiocyanate in refluxing dry acetone to afford new 2-iminothiazolidin-4-ones. The 5-arylidene-2-imino-3 (napthalen-2yl)- thiazolidin-4-ones were prepared by condensing 2-iminothiazolidin-4-ones with substituted benzaldehydes. All the products were characterized by infrared, mass, and 1H and 13C NMR techniques.
- Saravanan,Selvaraju,Nagarajan
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experimental part
p. 3361 - 3367
(2012/09/11)
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- Synthesis and biological evaluation of Matijing-Su derivatives as potent anti-HBV agents
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A series of Matijing-Su (MTS, N-(N-benzoyl-l-phenylalanyl)-O-acetyl-l- phenylalanol) derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity in 2.2.15 cells. The IC50 of compounds 14a (0.71 μM), 13c (2.85 μM), 13b (4.37 μM), etc. and the selective index of 13g (161.01), 13c (90.45), 13a (85.09) etc. of the inhibition on the replication of HBV DNA were better than those of the positive control lamivudine (IC50: 82.42 μM, SI: 41.59). Compounds 13o, 13p, and 16a also exhibited significant anti-HBV activity.
- Qiu, Jingying,Xu, Bixue,Huang, Zhengming,Pan, Weidong,Cao, Peixue,Liu, Changxiao,Hao, Xiaojiang,Song, Baoan,Liang, Guangyi
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experimental part
p. 5352 - 5360
(2011/10/12)
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- Synthesis and biological studies of N-phenyl substituted 2-(-5-(pyridine-4-yl)-1,3,4-oxadiazole-2-yl thio)acetamides
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As oxadiazole have proven to be good antimicrobial agents, Antitubercular, analgesic (peripheral and central) and antiinflammatory agents. A new series of oxadiazole derivatives were synthesized and characterized by 1H NMR, IR, GCMS sophisticated analytical instruments and were evaluated for their antimicrobial activity, antitubercular activity, toxicity as per standard guidelines, analgesic (peripheral and central) and antiinflammatory activity. Out of several derivatives synthesized a few of N-phenyl substituted 2-(5-(pyridine-4- yl)-1,3,4-oxadiazole-2-yl thio)acetamide explores good antimicrobial activity by using Cup-Plate method, antitubercular activity by middle brook 7H9 agar medium against H37Rv, analgesic activity by Writhing and Tail immersion method and antiinflammatory by rat paw edema method.
- Rao, M.E. Bhanoji,Rajurkar, Vikas G.
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experimental part
p. 2648 - 2652
(2012/01/05)
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- Synthesis and analgesic effects of 2-(2-carboxyphenylsulfanyl)-N-(4- substitutedphenyl)acetamide derivatives
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This present study was undertaken to synthesize and investigate possible analgesic activities of some 2-(2-carboxyphenylsulfanyl)-N-(4-substitutedphenyl) acetamide derivatives that were designed by combining an analgesic drug thiosalicylic acid and the ma
- Demir Oezkay, Uemide,Oezkay, Yusuf,Can, Oezguer Devrim
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scheme or table
p. 152 - 157
(2012/03/10)
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- Novel substituted and fused pyrrolizine derivatives: Synthesis, anti-inflammatory and ulcerogenecity studies
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Synthesis of several substituted pyrrolizines 10a-f, 11a-f, 13a-c, pyrimidopyrrolizines 14a-c, 15a-c, and pyrrolizinopyrimidoisoindoles 12a-c was discussed. The starting compounds 6-amino-7-cyano-N-(4-(un)substitutedphenyl)-2,3-dihydro-1H-pyrrolizine-5 -c
- Abbas, Safinaz E.,Awadallah, Fadi M.,Ibrahim, Nashwa A.,Gouda, Ahmed M.
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scheme or table
p. 482 - 491
(2010/04/02)
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- PHENYLALANINE DIPEPTIDE DERIVATIVES, COMPOSITIONS AND USE THEREOF
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Disclosed are a compound of formula I, stereoisomers, pharmaceutically acceptable salts or hydrates thereof, a pharmaceutical composition comprising the smae, a process for preparing the same and use thereof. The compound may also be used to prepare a medicament to treat viral infections, especially to prepare a medicament to treat hepatitis B virus and human immunodeficiency virus with little toxic side effects.
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Page/Page column 13
(2009/10/06)
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- Synthesis of α-chloroamides in water
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The reaction between chloroacetyl chloride and mono- or bis-aliphatic or aromatic amines in water under basic or neutral conditions gives rise to the formation of a variety of functionalized α-chloroamides. The resulting products were obtained as solids in moderate to good yields, upon precipitation and isolation by filtration.
- Harte, Andrew J.,Gunnlaugsson, Thorfinnur
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p. 6321 - 6324
(2007/10/03)
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- N-benzoyl>glycines as Mucolytic Agents
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m- and p-aminobenzoic acids were converted to the title compounds by sequential use of ClCH2COCl, SOCl2, glycine methyl or ethyl ester, AcSK, and hydrolysis.The title compounds and a number of salts were compared for mucolytic activity, toxicity, stabilit
- Martin, Tellis A.,Comer, William T.
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p. 910 - 914
(2007/10/02)
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