109492-62-8Relevant articles and documents
Synthesis of Spiro-Pyrrolidinyloxindoles by Oxidative Rearrangement of N-Acyltetrahydro-β-carbolines Using an Oxone/Aqueous Acetone Mixture
Mar?al, Luisa L.,Garden, Simon J.
, p. 19 - 32 (2019)
Spiro-pyrrolidinyl-2-oxindoles were prepared by the oxidative rearrangement of Na-acetyl-1,2,3,4-tetrahydro-β-carbolines (THBC) using dimethyldioxirane generated in situ. The Na-acetyl THBC substrates were obtained by Pictet-Spengler and acyl-Pictet-Spengler reactions of L-tryptophan methyl ester, followed by Na-acetylation. The stereoselectivity of the oxidative rearrangement was evaluated and 2D nuclear magnetic resonance (NMR) was used to determine the stereochemistry of the oxindole products relative to L-tryptophan. Density functional theory calculations were consistent with a face selective, substrate controlled, epoxidation of the indolic double bond. The calculations indicated that the resulting epoxide would readily rearrange at room temperature via a concerted ring opening/ring contraction process to give the 3-substituted-2-oxindole.
Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrugs of 5-aminosalicylic acid for colon-specific drug delivery in inflammatory bowel disease
Dhaneshwar, Suneela S.,Gairola, Neha,Kandpal, Mini,Vadnerkar, Gaurav,Bhatt, Lokesh,Rathi, Badal,Kadam
, p. 3922 - 3929 (2009)
Colon-specific mutual azo prodrugs of 5-aminosalicylic acid with essential amino acids were synthesized for the management of inflammatory bowel disease. The structures were confirmed by elemental and spectral analyses. 85-88% release of 5-aminosalicylic acid was achieved in rat fecal matter with half-lives ranging from 140 to 160 min, following first order kinetics. The prodrugs exhibited comparable ameliorating effect as that of sulfasalazine on trinitrobenzenesulfonic acid-induced experimental colitis in rats with a better safety profile.
Design, synthesis and bio-evaluation of C-1 alkylated tetrahydro-β-carboline derivatives as novel antifungal lead compounds
Singh, Rahul,Jaisingh, Aanchal,Maurya, Indresh K.,Salunke, Deepak B.
, (2020)
The field of antifungal agent has become static and development of resistance by the pathogen as well as limited clinical efficacy of marketed drugs demand the constant development of new antifungals. The presence of hydrocarbon chain of specific length linked with various different heterocycles was found to be an important structural feature in various antifungal lead compounds. Based on the prominent antimicrobial activity of β-carboline derivatives, a set of C1 alkylated tetrahydro-β-carboline derivatives were proposed to be active against fungi. To validate and confirm the role of suitable alkyl chains linked to a β-carboline scaffold, few related analogues having C1 aryl substituents were also synthesized in one step via classic Pictet-Spengler reaction. The synthesized library was evaluated for its antifungal activity against C. albicans, C. krusei, C. parapsilosis, C. kefyr, C. glabrata, C. tropicalis and C. neoformans. One of the library members (compound 12c), with n-alkyl chain of eight carbons exhibited potent antifungal activity against C. glabrata and C. kefyr. The lead compound, being selectively toxic also demonstrated prominent synergy enhancing the potency of antifungal drugs up to 10-fold. The time kill kinetic studies confirmed the efficacy of compound 12c, where the results obtained were comparable to that of Amp B. FE-SEM analysis revealed the increased asymmetry, disintegration and roughness of cell surface which could be because of the possible interaction of compound 12c at membrane level or interference in cell wall structure. Apoptosis/necrosis detection assay confirmed the significant apoptotic activity in C. glabrata cells after 12c treatment which was responsible for the rapid killing of C. glabrata cells.
Microwave assisted stereospecific synthesis of (S)-3-substituted 2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido [3,4-b]indole-1,4-diones
Pandey, Suresh K.,Awasthi, Keshav K.,Saxena, Anil K.
, p. 4437 - 4442 (2001)
A new easy way of preparing (S)-3-substituted 2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b] indole-1,4-diones, an important intermediate compound, is described using microwave irradiation supported on silica gel. The reaction is generalised and good to excellent yields of enantiomerically pure products are obtained.
Hydroxyphosphinylacetic acid as a chiral auxiliary compound
Majewska, Paulina
, p. 585 - 590 (2019)
The aim of the presented research was to check whether 2-hydroxy-2-(ethoxyphenylphosphinyl)acetic acid is a versatile chiral phosphonic auxiliary (readily seen in 31P NMR). The preliminary studies indicate that this compound may be used as chiral derivatizing agents for amines and alcohols, since the separation of selected examples of diastereomeric alcohols and amines in 31P NMR spectra was found to be satisfactory. The preliminary research about using this compound as a CSA are also promising.
Synthesis of New Chiral Auxiliaries Derived from (S)-Tryptophan
Cardillo, Giuliana,Gentilucci, Luca,Tomasini, Claudia,Tomasoni, Laura
, p. 1947 - 1956 (1995)
The synthesis of chiral aminoalcohols 4 derived from (S)-tryptophan is described, by reaction of the protected amino acid 3 with various Grignard reagents.The aminoalcohols were transformed into the corresponding oxazolidin-2-ones 2 and acylated with 2-butenoyl chloride and 2-hexenoyl chloride, affording the imides 5a-e.The conformational analysis of both the oxazolidin-2-ones 2 and the Michael acceptors 5 was performed by means of 1H NMR, NOEDIF experiments and semiempirical AM1 calculations.
A simple, high-yielding synthesis of N-t-butoxycarbonyl α-amino esters: Precursors for α-amino aldehydes
McNulty,Still
, p. 979 - 985 (1992)
A general one-pot, two-stage procedure is described for the preparation of the title compounds from the free amino acids in near quantitative yields.
Nano cuboids: Impact of 8-hydroxyquinoline on tryptophan properties and its applications
Sharma, Poonam,Singh, Prabhpreet
, (2020)
N-terminal tryptophan residues can be labeled with fluorophore by chemical reaction. Here in we report conjugation of 8-hydroxyquinoline (as fluorophore) with tryptophan using Schiff-base condensation reaction to decipher the impact of 8-hydroxyquinoline on the fluorescence and self-assembly properties of tryptophan in water. This water-soluble hydroxyquinoline–tryptophan (HQ-W1) conjugate has been demonstrated to have Aggregation Induced Emission (AIE) phenomena in water. HQ-W1 undergo spontaneous self-assembly to form nano cuboidal superstructures having 200–500 nm diameter and 300–650 nm length. In metal-ion binding studies this HQ-W1 shows selective fluorescence enhancement (14.5-fold) in the presence of Al3+ ions. The detection limit is 3.0 nM (UV method) and 3.53 nM (FI method). The AIE utility of HQ-W1 has been demonstrated by developing latent fingerprints.
Design and synthesis of novel monoterpenoid indole alkaloid-like analogues and their antitumour activities: In vitro
Fang, Jiaqi,Huang, Tao,Xia, Mengyuan,Deng, Lulu,Hao, Xiaojiang,Wang, Yuehu,Mu, Shuzhen
, p. 3026 - 3037 (2018)
A biomimetic synthetic strategy and combinatorial chemistry were used to synthesize 34 novel monoterpenoid indole alkaloid (MIA) analogues, and their cytotoxic activities against five cancer cell lines (SW-480, A-549, HL-60, SMMC-7721, and MCF-7) were determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Fourteen of these analogues (7, 16-18, and 23-32) showed significantly greater inhibition of tumour cell proliferation than cisplatin. Compounds 17 and 18 showed the highest cytotoxic activity against the HL-60 cell line with IC50 values of 0.90 μM and 0.43 μM, respectively. Compound 18 slightly induced apoptosis and arrested the cell cycle in SW-480, A-549, HL-60, SMMC-7721, and MCF-7 cells. Analysis of the primary structure-activity relationships reveals that the introduction of different substituent groups at the C-3, C-5, and C-6 positions of the indole moiety and the C-10 position of the genipin moiety might have an effect on the antitumour activity of the resulting compounds.
Synthesis and characterization of new 2-substituted isoindoline derivatives of α-amino acids
Mancilla, Teresa,Carrillo, Lourdes,Zamudio-Rivera, Luis S.,Beltran, Hiram I.,Farfan, Norberto
, p. 341 - 349 (2001)
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Enhancement of the chiroptical response of α-amino acids via N-substitution for molecular structure determination using vibrational circular dichroism
Polavarapu, Prasad L.,Santoro, Ernesto,Covington, Cody L.,Raghavan, Vijay
, p. 564 - 578 (2020)
The chiroptical response in the form of vibrational circular dichroism (VCD) in the midinfrared region is found to be enhanced when a hydrogen of amino group of l-tryptophan is substituted with acetyl, acryloyl, or maleyl group. The order of preference for VCD enhancement is found to be acryloyl > acetyl > maleyl group. The resulting experimental VCD spectra are also found to be satisfactorily reproduced by the quantum mechanical (QM) predicted spectra. The QM predicted spectra were simulated using the conformer populations, (a) predicted by Gibbs energies and (b) optimized to maximize the similarity between experimental and predicted VCD spectra. It is found that the conformer populations predicted by Gibbs energies do not yield the maximum possible similarity between experimental and the QM predicted spectra. This work identifies the N-substitution of α-amino acids and determining the conformer populations that best reproduce the experimental spectra as two new approaches for molecular structure determination.
Synthesis and pharmacological evaluation of mutual prodrugs of aceclofenac with quercetin, vanillin and l-tryptophan as gastrosparing NSAIDS
Rasheed, Arun,Lathika,Raju, Y. Prasanna,Mansoor,Azeem,Balan, Nija
, p. 70 - 82 (2016)
Synthesis, physicochemical characterization and pharmacological evaluation of mutual prodrugs of aceclofenac with quercetin, vanillin and l-tryptophan have been attempted to develop novel gastrosparing NSAIDs, devoid of ulcerogenic side effects. The structures of synthesized prodrugs were confirmed by IR, 1H NMR, 13C NMR and mass spectroscopy. The hydrolysis kinetics studies were performed in simulated gastric fluid, simulated intestinal fluid and rat fecal matter. Its anti-inflammatory and ulcer index were analyzed along with estimation of biochemical parameters (GWM and Hexosamine), oxidative parameters (LPO, GSH, CAT, and SOD) and protein estimation. The results indicated that the synthesized prodrugs are chemically stable, biolabile and possesses optimum lipophilicity. They also exhibited retention of anti-inflammatory activity with reduced ulcerogenicity. The study showed that the mutual prodrugs are better in action compared to the parent drug and have fewer gastrointestinal side effects.
Synthesis and antimalarial activity of (S)-methyl-(7-chloroquinolin-4-ylthio)acetamidoalquilate derivatives
Colmenarez, Custodiana,Acosta, María,Rodríguez, Miguel,Charris, Jaime
, p. 161 - 166 (2020)
The synthesis of five new (S)-methyl-(7-chloroquinolin-4-ylthio)acetamidoalquilate derivatives is carried out under a modified version of the Steglich esterification reaction between different l-amino acid methyl esters and 2-(7-chloroquinolin-4-ylthio)acetic acid. Two of the compounds showed significant inhibition (>50%) of β-hematin formation. The two active structures were tested in vivo as potential antimalarials in mice infected with Plasmodium berghei ANKA, a chloroquine susceptible strain. Compounds 6b and 6e exhibited antimalarial activity comparable to that of chloroquine.
Discovery of novel β-carboline/acylhydrazone hybrids as potent antitumor agents and overcome drug resistance
Li, Yong,Yan, Wei,Yang, Jianhong,Yang, Zhuang,Hu, Mengshi,Bai, Peng,Tang, Minghai,Chen, Lijuan
, p. 516 - 526 (2018)
Twenty-four novel β-carboline/acylhydrazone hybrids were synthesized and evaluated for their in vitro antiproliferative activity. Among them, 12r exhibited the most potent activity, with IC50 values of 1–2 μM against panel of cancer cell lines and retained significant activity in multidrug resistant cancer cells. Treated cells were not arrested in any phase of cell cycle but resulted in late cellular apoptosis on both MCF-7 and MCF-7/ADR cancer cells. Importantly, 12r showed certain antitumor effect on inhibiting the tumor growth with low toxic and side effects and without significant body weight loss.
Cu-Catalyzed Site-Selective C(sp2)-H Radical Trifluoromethylation of Tryptophan-Containing Peptides
Correa, Arkaitz,Guerrero, Itziar
, p. 1754 - 1759 (2020)
Site-selective functionalization of C-H bonds within a peptide framework poses a challenging task of paramount synthetic relevance. Herein, we report an operationally simple C(sp2)-H trifluoromethylation of tryptophan (Trp)-containing peptides. This fluorination technique is characterized by its chirality preservation, tolerance of functional groups, and scalability and exhibits chemoselectivity for Trp residues over other amino acid and heterocyclic units. As a result, it represents a sustainable tool toward the late-stage peptide modification and protein engineering.
Convenient method for the synthesis of some novel chiral methyl 2-(2-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)propanoate derivatives and biological evaluation of their antioxidant, cytotoxic, and molecular docking properties
Matam, Sivakumar,Kaliyan, Prabakaran,Selvaraj, Loganathan,Muthu, Seenivasa Perumal,Lohanathan, Bharathi Priya,Viswanadhan, Vijaya Padma,Makala, Himesh,Venkatasubramanian, Ulaganathan
supporting information, p. 569 - 579 (2020/12/11)
Ten chiral methyl 2-(2-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)propanoate derivatives 6a-6j have been synthesized from optically pure amino methyl phenol 5 and 4-nitrophenyl chloroformate. These derivatives 6a-6j are characterized by 1H NMR, 13C NMR, FT-IR, and HRMS spectral techniques. Optical purity of these derivatives was confirmed by chiral HPLC method. Ten synthesized ester derivatives 6a-6j were screened for their in vitro antioxidant activity. Among the compounds 6b-d and 6h-j have exhibited comparable antioxidant activity with ascorbic acid as a standard. Compounds 6a and 6e-g have shown moderate antioxidant activity. Further, the in vitro cytotoxicity of these compounds were studied through MTT cell proliferation assay in addition the effect on LDH leakage and NO release. Among the derivatives, 6j showed extremely best activity and the IC50 value (12.54 ± 0.71 μM) is very close to doxorubicin (7.2 ± 0.58 μM) as a standard. Compounds 6b, 6h, and 6i showed better inhibition next to compound 6j on the viability of HepG2 cells with an IC50 value (μM) of 56.02 ± 1.4, 41.76 ± 0.58, and 38.17 ± 0.34, respectively. Also, molecular docking studies have been carried out with STAT-3 (PDB ID: 1BG1) and BCL-2 (PDB ID: 4AQ3) proteins against the four active compounds 6b, 6h, 6i, and 6j. The binding energies of the tested compounds were in the range of ?7.76 to ?8.41 kcal/mol, which is very close to doxorubicin (?8.53 kcal/mol) as a standard. These molecular docking results are in good agreement with the in vitro studies.
Translation of Mycobacterium Survival Strategy to Develop a Lipo-peptide based Fusion Inhibitor**
Sardar, Avijit,Lahiri, Aritraa,Kamble, Mithila,Mallick, Amirul I.,Tarafdar, Pradip K.
supporting information, p. 6101 - 6106 (2021/02/01)
The entry of enveloped virus requires the fusion of viral and host cell membranes. An effective fusion inhibitor aiming at impeding such membrane fusion may emerge as a broad-spectrum antiviral agent against a wide range of viral infections. Mycobacterium survives inside the phagosome by inhibiting phagosome–lysosome fusion with the help of a coat protein coronin 1. Structural analysis of coronin 1 and other WD40-repeat protein suggest that the trp-asp (WD) sequence is placed at distorted β-meander motif (more exposed) in coronin 1. The unique structural feature of coronin 1 was explored to identify a simple lipo-peptide sequence (myr-WD), which effectively inhibits membrane fusion by modulating the interfacial order, water penetration, and surface potential. The mycobacterium inspired lipo-dipeptide was successfully tested to combat type 1 influenza virus (H1N1) and murine coronavirus infections as a potential broad-spectrum antiviral agent.
