Divya Mathur

Biocatalytic route to sugar-PEG-based polymers for drug delivery applications.

Sugar-PEG-based polymers were synthesized by enzymatic copolymerization of 4-C-hydroxymethyl-1,2-O-isopropylidene-β-L-threo-pentofuranose/4-C-hydroxymethyl-1,2-O-benzylidene-β-L-threo-pentofuranose/4-C-hydroxymethyl-1,2-O-isopropylidene-3-O-pentyl-β-L-threo-pentofuranose with PEG-600 dimethyl ester using Novozyme-435 (Candida antarctica lipase immobilized on polyacrylate). Carbohydrate monomers were obtained by the multistep synthesis starting from diacetone-D-glucose and PEG-600 dimethyl ester, which was in turn obtained by the esterification of the commercially available PEG-600 diacid. Aggregation studies on the copolymers revealed that in aqueous solution those polymers bearing the hydrophobic pentyl/benzylidene moiety spontaneously self-assembled into supramolecular aggregates. The critical aggregation concentration (CAC) of polymers was determined by surface tension measurements, and the precise size of the aggregates was obtained by dynamic light scattering. The polymeric aggregates were further explored for their drug encapsulation properties in buffered aqueous solution of pH 7.4 (37 °C) using nile red as a hydrophobic model compound by means of UV/vis and fluorescence spectroscopy. There was no significant encapsulation in polymer synthesized from 4-C-hydroxymethyl-1,2-O-isopropylidene-β-L-threo-pentofuranose because this sugar monomer does not contain a big hydrophobic moiety as the pentyl or the benzylidene moiety. Nile red release study was performed at pH 5.0 and 7.4 using fluorescence spectroscopy. The release of nile red from the polymer bearing benzylidene moiety and pentyl moiety was observed with a half life of 3.4 and 2.0 h, respectively at pH 5.0, whereas no release was found at pH 7.4.

Structure-activity relationship studies of 4-methylcoumarin derivatives as anticancer agents

Abstract Context: Cancer is a leading cause of death worldwide and novel chemotherapeutic agents with better efficacy and safety profiles are much needed. Coumarins are natural polyphenolic compounds with important pharmacological activities, which are present in many dietary plants and herbal remedies. Objectives: The objective of this study is to investigate natural and synthetic coumarin derivatives with considerable anticancer capacity against three human cancer cell lines. Materials and methods: We synthesized 27 coumarin derivatives (mostly having 4-methyl moiety) and examined their cytotoxic effect on three human cancer cell lines, K562 (chronic myelogenous leukemia), LS180 (colon adenocarcinoma), and MCF-7 (breast adenocarcinoma) by MTT reduction assay. Screened compounds included 7-hydroxy-4-methylcoumarins (7-HMCs), 7-acetoxy-4-methylcoumarins (7-AMCs), and different dihydroxy-4-methylcoumarin (DHMC) and diacetoxy-4-methylcoumarin (DAMC) derivatives. Some compounds with methoxy, amine, and bromine substitutions were also examined. Results: 7,8-DHMCs bearing alkyl groups at C3 position were the most effective subgroup, and of which, the most potent is compound 11, with an n-decyl chain at C3, which had IC50 values of 42.4, 25.2, and 25.1 µM against K562, LS180, and MCF-7 cells, respectively. The second most active subgroup was 7,8-DAMCs containing ethoxycarbonylmethyl and ethoxycarbonylethyl moieties at C3 position. Compound 27 (6-bromo-4-bromomethyl-7-hydroxycoumarin), the only derivative containing bromine also showed reasonable cytotoxic activities (IC50 range: 32.7–45.8 µM). Discussion and conclusion: This structure–activity relationship (SAR) study of 4-methylcoumarins shows that further investigation of these derivatives may lead to the discovery of novel anticancer agents.

Chemoenzymatic synthesis of 3'-deoxy-3'-(4-substituted-triazol-1-YL)-5-methyluridine.

An efficient protocol has been developed for the synthesis of a small library of 3′-deoxy-3′-(4-substituted-triazol-1-yl)-5-methyluridine using Cu(I)-catalyzed Huisgen–Sharpless–Meldal 1,3-dipolar cycloaddition reaction of 3′-azido-3′-deoxy-5-methyluridine with different alkynes under optimized condition in an overall yields of 76%–92%. Here, the azido precursor compound, i.e., 3′-azido-3′-deoxy-5-methyluridine was chemoenzymatically synthesized from D-xylose in good yield. Some of the alkynes used in cycloaddition reaction were synthesized by the reaction of hydroxycoumarins or naphthols with propargyl bromide in acetone using K2CO3in excellent yields. All synthesized compounds were unambiguously identified on the basis of their spectral (IR, 1H-, 13C NMR spectra, and high-resolution mass spectra) data analysis.

Biocatalytic Synthesis of Novel Partial Esters of a Bioactive Dihydroxy 4-Methylcoumarin by Rhizopus oryzae Lipase (ROL)

Highly regioselective acylation has been observed in 7,8-dihydroxy-4-methylcoumarin (DHMC) by the lipase from Rhizopus oryzae suspended in tetrahydrofuran (THF) at 45 °C using six different acid anhydrides as acylating agents. The acylation occurred regioselectively at one of the two hydroxy groups of the coumarin moiety resulting in the formation of 8-acyloxy-7-hydroxy-4-methylcoumarins, which are important bioactive molecules for studying biotansformations in animals, and are otherwise very difficult to obtain by only chemical steps. Six monoacylated, monohydroxy 4-methylcoumarins have been biocatalytically synthesised and identified on the basis of their spectral data and X-ray crystal analysis.

Recent Progress in the Chemistry of Tri-substituted Triazole via [3 + 2] Cycloaddition of Azide and Double Bond: An Overview

Triazoles belong to a class of nitrogen containing compounds which are known for its highly valuable and versatile biological activities. More than 50 years ago, the first synthesis of tri-substituted triazoles was achieved by Huisgen via azide-alkyne cycloaddition. Over the years the remarkable achievement in triazole-based pharmacology promoted ample interest in the discovery of new synthetic methods and catalysts for the synthesis of this miraculous scaffold. Recent tri-substituted triazoles development based on various azides and double bonds have been summarized in this report.

Recent Advances in Triazolyl Nucleosides

Nucleosides and its modified analogues are important components and possess key roles in various biological processes. Copper catalyzed 1,3-dipolar cycloadditions have been emerged as an excellent tool to join azide and alkyne moieties to form triazolyl compounds. Presence of triazole group enhances the therapeutic potential as well as fluorescence properties of the modified nucleosides. Owing to the designing and development of the new triazolyl nucleosides for their various biological and photophysical application at faster pace, there is a need to have knowledge of the recent developments in this area. The review herein highlights the various modifications, therapeutic importance and other applications of recently reported triazolyl-nucleosides.