- Diazaborines Are a Versatile Platform to Develop ROS-Responsive Antibody Drug Conjugates**
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Antibody–drug conjugates (ADCs) are a new class of therapeutics that combine the lethality of potent cytotoxic drugs with the targeting ability of antibodies to selectively deliver drugs to cancer cells. In this study we show for the first time the synthesis of a reactive-oxygen-species (ROS)-responsive ADC (VL-DAB31-SN-38) that is highly selective and cytotoxic to B-cell lymphoma (CLBL-1 cell line, IC50 value of 54.1 nM). The synthesis of this ADC was possible due to the discovery that diazaborines (DABs) are a very effective ROS-responsive unit that are also very stable in buffer and in plasma. DFT calculations performed on this system revealed a favorable energetic profile (ΔGR=?74.3 kcal mol?1) similar to the oxidation mechanism of aromatic boronic acids. DABs’ very fast formation rate and modularity enabled the construction of different ROS-responsive linkers featuring self-immolative modules, bioorthogonal functions, and bioconjugation handles. These structures were used in the site-selective functionalization of a VL antibody domain and in the construction of the homogeneous ADC.
- Aguiar, Sandra I.,André, Ana S.,António, Jo?o P. M.,Bernardes, Gon?alo J. L.,Carvalho, Joana Inês,Dias, Joana N. R.,Faustino, Hélio,Gois, Pedro M. P.,Lopes, Ricardo M. R. M.,Veiros, Luis F.,da Silva, Frederico A.
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supporting information
p. 25914 - 25921
(2021/11/09)
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- Synthesis and characterization of hydrazone and azine derivatives of bis(cyclopentadienyI) titanium(IV)
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Pentacoordinated hydrazone and azine derivatives of bis(cyclopentadienyl)titanium(IV) of the type {equation presented}, have been prepared. The products were characterized by chemical analyses, elec- trical conductance, IR, 1H NMR, and electronic spectral studies. Some hydrazone complexes and a few azine com- plexes of titanium have been studied.' ' However, no systematic study on their organometallic derivatives is available. In view of the versatile chelating ability, widespread applications and lack of data involving organometallic derivatives of titanium, it has been considered of interest to study the reactions of Cp2TiCl2 with the title ligands.
- Kaushik, Narender Kumar,Khera, Brij,Sharma, Anand Kumar
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p. 793 - 794
(2021/11/22)
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- New library of pyrazole–imidazo[1,2-α]pyridine molecular conjugates: Synthesis, antibacterial activity and molecular docking studies
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A library of novel pyrazole–imidazo[1,2-α]pyridine scaffolds was designed and synthesized through a one-pot three-component tandem reaction. The structures of synthesized conjugates were confirmed by spectroscopic techniques (NMR, IR and HRMS). In vitro antibacterial evaluation of the twelve synthesized molecules (7a, 8a–k) against methicillin-resistant Staphylococcus aureus and normal strains of Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia and Pseudomonas aeruginosa established 8b, 8d, 8e, 8h and 8i as potent antibacterial agents with superior minimum bactericidal concentration, compared with standard drug ciprofloxacin. Molecular docking studies of all active compounds into the binding site of glucosamine-6-phosphate synthase were further performed in order to have a comprehensive understanding of putative binding modes within the active sites of the receptor.
- Ebenezer, Oluwakemi,Awolade, Paul,Koorbanally, Neil,Singh, Parvesh
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p. 162 - 173
(2019/11/03)
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- Ultrasonic assisted synthesis of 2, 3-dihydroquinazolin-4(1H)-ones involving three-component reaction of isatoic anhydride, amines and pyrazole carbaldehydes catalyzed by [?-fe2o3?hap-So3H]
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The combination of [?-Fe2O3?HAp-SO3H] as a catalyst and ultrasonic effect catalyzed the synthesis of diverse derivatives of 2, 3-dihydroquinazolin-4(1H)-ones which is reported in this study. The products were synthesized via the one-pot three-component reaction of isatoic anhydride, amines and pyrazole carbaldehydes in water: EtOH catalyzed by recoverable [?-Fe2O3?HAp-SO3H]. This paper conducted an investigation of the effect of various solvents, temperatures and catalysts on the reactions. Short reaction times, mild reaction conditions, simple work-up, the desired yields and the use of an appropriate catalyst are the advantages of this novel method. The new derivatives were validated by using FT-IR,1HNMR, and13CNMR. Moreover, the synthesized compounds were screened for their an-timicrobial activity against bacterial strains.
- Mahmoodi, Nosrat O.,Moghadam, Kurosh R.,Nikpassand, Mohammad,Rasa, Mahdi,Sina, Kiana F.,Yahyazadeh, Asieh
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- AlCl3·6H2O-catalyzed Schiff-base reaction between aryl ketones and aromatic acylhydrazines/hydrazines in water
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Abstract: Schiff-bases have important applications in the field of analysis, biomedicine, as well as material sciences. Hydrazones and acylhydrazones are two representative types of Schiff-bases. In this study, a green synthesis of aromatic hydrazones and
- Zhao, Zhi Xiang,Li, Ting,Cheng, Li Ping,Li, Meng,Zhong, Zhi Jian,Pang, Wan
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p. 1833 - 1839
(2019/11/05)
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- Synthesis and Antimicrobial Activities of Novel 2-[substituted-1H-pyrazol-4-yl] Benzothiazoles, Benzoxazoles, and Benzimidazoles
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In an endeavor to find a new class of antimicrobial agents, a series of novel substituted benzimidazole, benzoxazole, and benzothiazole derivatives 6 containing pyrazole moiety have been synthesized by reaction of 3-aryl-4-formyl pyrazole 4 with substitut
- Padalkar, Vikas S.,Borse, Bhushan N.,Gupta, Vinod D.,Phatangare, Kiran R.,Patil, Vikas S.,Sekar, Nagaian
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p. 1347 - 1355
(2016/09/23)
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- Synthesis and Antimicrobial Evaluation of Novel Pyrazole-Annulated Oxygen-Containing Macrocycles
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[Figure not available: see fulltext.] An efficient approach to the synthesis of fused pyrazole-annulated macrocycles has been demonstrated. Vilsmeier–Haack reaction of substituted o-hydroxyacetophenones with phenyl hydrazine followed by reduction of the r
- Ashok, Dongamanti,Devulapally, Mohan Gandhi,Gundu, Srinivas,Aamate, Vikas Kumar,Chintalapally, Shivakanth
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p. 609 - 614
(2017/03/16)
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- Identification of novel pyrazole-rhodanine hybrid scaffolds as potent inhibitors of aldose reductase: Design, synthesis, biological evaluation and molecular docking analysis
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In an effort to develop a new class of potent aldose reductase inhibitors, a series of 1,3-diarylpyrazole assimilated 3-substituted 4-oxo-2-thioxo-1,3-thiazolidines (9a-n) was designed, and synthesized in good to excellent yields by a pharmacophore integr
- Andleeb, Hina,Tehseen, Yildiz,Ali Shah, Syed Jawad,Khan, Imtiaz,Iqbal, Jamshed,Hameed, Shahid
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p. 77688 - 77700
(2018/06/22)
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- Synthesis, antiviral, cytotoxicity and antitumor evaluations of A4 type of porphyrin derivatives
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This manuscript describes the synthesis of a new series of porphyrin structures 4a-4m, 7, 9, 12 and 14. These structures were investigated against two types of viruses such as HIV-1 and HSV-1. Also they were screened for their antitumor activity. Among all tested compounds, it was found that compound 4b showed a high activity against HIV-1 and HSV-1 and against four different tumor cell lines. Most of the tested compounds showed a moderate degree of a potent antimicrobial activity. The structure of these compounds was confirmed on the basis of their analytical and spectral data such as UV-vis, IR, 13C NMR, 1H NMR spectroscopy and mass spectral data.
- Fadda, Ahmed A.,El-Mekawy, Rasha E.,El-Shafei, Ahmed I.
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p. 753 - 768
(2015/10/29)
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- Synthesis, antiviral, cytotoxicity and antitumor evaluations of A4 type of porphyrin derivatives
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This manuscript describes the synthesis of a new series of porphyrin structures 4a-4m, 7, 9, 12 and 14. These structures were investigated against two types of viruses such as HIV-1 and HSV-1. Also they were screened for their antitumor activity. Among all tested compounds, it was found that compound 4b showed a high activity against HIV-1 and HSV-1 and against four different tumor cell lines. Most of the tested compounds showed a moderate degree of a potent antimicrobial activity. The structure of these compounds was confirmed on the basis of their analytical and spectral data such as UV-vis, IR, 13C NMR, 1H NMR spectroscopy and mass spectral data.
- Fadda, Ahmed A.,El-Mekawy, Rasha E.,El-Shafei, Ahmed I.
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p. 753 - 768
(2016/01/09)
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- Synthesis, docking and pharmacological evaluation of novel indole based potential atypical antipsychotics
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A series of substituted indole derivatives have been synthesized and the target compounds evaluated for atypical antipsychotic activity in apomorphine induced mesh climbing and stereotypy assays in mice. The compounds 11 and 12 have emerged as important l
- Bali, Alka,Sen, Umesh,Peshin, Tania
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p. 477 - 490
(2014/03/21)
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- Novel and efficient synthesis of 4-indazolyl-1,3,4-trisubstituted pyrazole derivatives
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In the present study, 1-(4,5-dihydro-3,6-dimethyl-4-(1,3-diphenyl-1H- pyrazol-4-yl)-3aH-indazol-5-yl)methanone derivatives (9-12) and isoxazoleyl (13-16) have been synthesized by the condensation of 1,3-diphenyl-1H-pyrazole-4- carbaldehyde (1-4) with acetyl acetone via Knoevenagel/Michael/aldol reactions in a sequential manner to yield intermediate cyclohexanone (5-8). The intermediates (5-8) treated with NH2NH2·H 2O/NH2OH·HCl afforded 4-indazolyl-1,3,4- trisubstituted pyrazole and isoxazoleyl derivatives. All of these compounds are reported for the first time, and the structures of these compounds were confirmed by means of infrared, 1H NMR, 13C NMR, and mass spectroscopy.
- Hote, Baliram S.,Lokhande, Pradeep D.
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p. 1492 - 1500
(2014/05/20)
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- Remote anionic fries rearrangement of sulfonates: Regioselective synthesis of indole triflones
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An unusual NaH-mediated remote anionic 1,5-thia-Fries rearrangement reaction was developed. This method provides an efficient approach for the regioselective synthesis of not only 2-(2-hydroxyphenyl)-3-indole triflones but also related 3-sulfonylindoles.
- Xu, Xiu-Hua,Taniguchi, Misaki,Azuma, Ayaka,Liu, Guo Kai,Tokunaga, Etsuko,Shibata, Norio
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supporting information
p. 686 - 689
(2013/03/29)
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- Curcumin-I Knoevenagel's condensates and their Schiff's bases as anticancer agents: Synthesis, pharmacological and simulation studies
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Pyrazolealdehydes (4a-d), Knoevenagel's condensates (5a-d) and Schiff's bases (6a-d) of curcumin-I were synthesized, purified and characterized. Hemolysis assays, cell line activities, DNA bindings and docking studies were carried out. These compounds were lesser hemolytic than standard drug doxorubicin. Minimum cell viability (MCF-7; wild) observed was 59% (1.0 μg/mL) whereas the DNA binding constants ranged from 1.4 × 10 3 to 8.1 × 105 M-1. The docking energies varied from -7.30 to -13.4 kcal/mol. It has been observed that DNA-compound adducts were stabilized by three governing forces (Van der Wall's, H-bonding and electrostatic attractions). It has also been observed that compounds 4a-d preferred to enter minor groove while 5a-d and 6a-d interacted with major grooves of DNA. The anticancer activities of the reported compounds might be due to their interactions with DNA. These results indicated the bright future of the reported compounds as anticancer agents.
- Ali, Imran,Haque, Ashanul,Saleem, Kishwar,Hsieh, Ming Fa
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p. 3808 - 3820
(2013/07/25)
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- Synthesis of novel pyrazolyl tetrazoles as selective COX-2 inhibitors
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A series of novel pyrazolyl tetrazoles were synthesized by introducing tetrazole moiety at the fourth position of 1,3-substituted pyrazole nucleus. Synthesis was carried out by cyclization of different pyrazolonitriles using sodium azide in the presence of triethylammonium chloride as phase transfer catalyst. The structures of the synthesized compounds were confirmed on the basis of physical and spectral data. Among the synthesized compounds, 4b and 4e displayed significant anti-inflammatory activity with no observable ulcerogenic effect when compared with diclofenac sodium. Furthermore, compounds 4b and 4e were found to have COX-2 selectivity with a ratio of 0.44 and 0.48, respectively.
- Swetha, Kolli Sri,Parameshwar, Ravula,Reddy, B. Madhava,Babu, V. Harinadha
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p. 4886 - 4892
(2013/09/23)
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- Efficient and rapid synthesis of highly functionalized novel symmetric 1,4-dihydropyridines using glacial acetic acid as solvent
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A new series of 1,4-dihydropyridines bearing a pyrazole moiety in the 4-position were synthesized by a variation of the classical Hantzsch synthesis. The reaction of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde 4a-n with 3-amino crotononitrile in the presence of glacial acetic acid afforded novel 3,5-dicyano-2,6-dimethyl 1,4-dihydropyridines 5a-n. The procedure has short reaction time (15-20 min), easy workup, and good yield of product. The structures of all synthesized compounds were well characterized by mass, infrared, 1H and 13C NMR, and elemental analysis.
- Thakrar, Shailesh,Bavishi, Abhay,Bhavsar, Dhairya,Parekh, Shrey,Vala, Hardev,Radadiya, Ashish,Parmar, Manisha,Savant, Mahesh,Shah, Anamik
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scheme or table
p. 3269 - 3278
(2012/09/08)
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- Crystal structure and quantum chemical calculations on o- hydroxyacetophenone phenylhydrazone
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o-Hydroxyacetophenone phenylhydrazone has been synthesized and characterized by elemental analysis, IR and electronic spectroscopy. The X-ray crystal structure study shows that the compound contains two crystallographically independent molecules in the asymmetric unit and crystallizes in the monoclinic system, space group P21/c1 with Mr = 226.27(C14H14N2O),a= 13.433(3), b=10.738(2),c= 18.351(7) A, β =114.44(2)°, V= 2409.8(12) A3, Z= 8, Dc = 1.247 Mg/m3, F (000) = 960, μ (Mo Kα) = 0.080 mm-1, R = 0.0638, wR = 0.1535. Ab initio calculations of the structure, atomic charge distributions, natural bond orbital analysis and thermodynamic functions of the title compound were performed at HF/6-311G** and B3LYP/6-311G** levels of theory. Electronic absorption spectra were calculated by the time-dependent density functional theory (TD-DFT). Vibrational frequencies were predicted, assigned and compared with the experimental values. The calculation of the second order optical nonlinearity was carried out and the molecular hyperpolarizability of 3.332?10-30 esu was predicted.
- Jian,Li,Yang,Zhao,Xiao
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p. 1597 - 1609
(2008/12/22)
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- A mild procedure for the preparation of 3-aryl-4-formylpyrazoles
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A variety of 3-aryl-4-formylpyrazoles can be easily prepared in good yields from the corresponding methyl ketones, upon treatment with 2,4,6-trichloro[1,3, 5]triazine in N,N-dimethyl formamide at room temperature. This kind of pyrazole can constitute new building blocks for combinatorial chemistry.
- De Luca, Lidia,Giacomelli, Giampaolo,Masala, Simonetta,Porcheddu, Andrea
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p. 2299 - 2302
(2007/10/03)
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- Oxygenation of 2,3-dihydroindoles
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Isatogens (3-oxo-3H-indole 1-oxides) possess interesting biological properties and development of a general method to construct these derivatives has now been developed. Indolines (2,3-dihydroindoles) and isatogens have been prepared in an efficient route starting from indoles substituted in position 2. Reduction of the 2-substituted indoles was performed with tin and hydrochloric acid to give racemic indolines, which were converted to isatogens by 3-chloroperoxybenzoic acid (m-CPBA).
- Sl?tt, Johnny,Bergman, Jan
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p. 9187 - 9191
(2007/10/03)
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- Ruthenium-(II)/-(III) terpyridine complexes incorporating imine functionalities. Synthesis, structure, spectroscopic and electrochemical properties
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A new class of ruthenium terpyridine complexes of the type [RuII(trpy)(L1-6)Cl] 1-6 (trpy=2,2':6',2''-terpyridine; L1-3=o--OC6H3(R)C(R')=NCH2C6H5 and L4-6=o--OC6H3(R)CH(R')N=NC6H5; where R=H or p-NO2 and R'=H or CH3) have been synthesized. The "free" ligands incorporating a NH spacer o--OC6H3(R)C(R')=NNHC6H5 (HL4-6) have undergone imine to azo tautomerism on co-ordination to the ruthenium terpyridine moiety in the complexes 4-6, whereas those having a CH2 spacer (HL1-3) remain unaltered on co-ordination. The diamagnetic, neutral complexes 1-6 exhibit strong MLCT transitions in the visible region and intraligand transitions in the UV region. A significant shift in MLCT band energy has been observed depending on the ligand field strength of the co-ordinated L. The complexes display a reversible ruthenium(III)-ruthenium (II) couple in the potential range of 0.12-0.63 V and a quasi-reversible ruthenium(IV)-ruthenium(III) couple in the range of 1.21-1.85 V versus SCE. The higher ligand field strength of the co-ordinated L4-6 compared to the co-ordinated L3- is reflected in the observed metal redox processes. The reduction of the co-ordinated terpyridine has been observed near -1.3 V. The complexes exhibit moderately strong emissions from the lowest energy MLCT bands in the range 661-690 nm in EtOH-MeOH (4:1 v/v) at 77 K. The quantum yields of the complexes (Φ=0.006-0.09) are found to be reasonably sensitive to the nature of the co-ordinated L. The oxidised complexes 3+ and 6+ have been isolated in the solid state as their perchlorate salts. The crystal structure of 3+ exhibits pseudo-octahedral trans geometry with regard to the relative disposition of the imine nitrogen (N4) of L3 and the central pyridyl group of the trpy ligand. The one-electron paramagnetic complexes show 1:1 conductivity and display ligand-to-metal charge transfer bands near 600 and 400 nm and intraligand transitions in the UV region. The observed rhombic EPR spectra at 77 K corresponding to the distorted octahedral geometry have been analysed to furnish values of axial (Δ) and rhombic (V) distortion parameters as well as the energies of the two expected ligand field transitions (ν1 and ν2) within the t2 shell.
- Mondal, Biplab,Chakraborty, Soma,Munshi, Pradip,Walawalkar, Mrinalini G.,Lahiri, Goutam Kumar
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p. 2327 - 2336
(2007/10/03)
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- The preparation of 2-(1-phenyl-5-phenyl or 5-substituted phenyl-1H- pyrazol-3-yl)phenols from trilithiated 2'-hydroxyacetophenone phenylhydrazone and aromatic esters
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2'-Hydroxyacetophenone phenylhydrazone was trilithiated with excess lithium diisopropylamide, and the resulting trianion-type intermediate was condensed with a variety of aromatic esters followed by acid cyclization to 2-(1-phenyl-5-phenyl or 5-substitute
- Rampey, Mary E.,Hurst, Douglas R.,Sood, Aseem,Studer-Martinez, Shannon L.,Beam, Charles F.
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p. 495 - 506
(2007/10/03)
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- Synthesis and Characterization of Hydrazone and Azine Derivatives of Bis(cyclopentadienyl)titanium(IV)
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Pentacoordinated hydrazone and azine derivatives of bis(cyclopentadienyl)titanium(IV) of the type and , where R=H or CH3, R'=H, C6H5 or C6H3(NO2)2 and R''=H or CH3 have been prepared.The products were characterized by chemical analyses, electrical conductance, IR, 1H NMR, and electronic spectral studies.
- Khera, Brij,Sharma, Anand Kumar,Kaushik, Narender Kumar
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p. 793 - 794
(2007/10/02)
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- Synthesis and characterization of hydrazone and azine derivatives of bis(cyclopentadienyl)zirconium(IV)
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Pentacoordinated hydrazone and azine derivatives of bis(cyclopentadienyl)zirconium(IV) of the type and , where R = H or CH3 and R' = H, C6H5 or C6H3(NO2)2, have been synthesized by the reaction of bis(cyclopentadienyl)zirconium(IV) dichloride with the appropriate hydrazone or azine in equimolar ratios in refluxing tetrahydrofuran.The products were characterized by chemical analyses, electrical conductance, IR, 1H NMR and electronic spectral studies.
- Khera, B.,Sharma, A. K.,Kaushik, N. K.
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p. 172 - 174
(2007/10/02)
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