Hardesh K. Maurya

Studies on substituted benzo[h]quinazolines, benzo[g]indazoles, pyrazoles, 2,6-diarylpyridines as anti-tubercular agents

Various substituted 5,6-dihydro-8-methoxybenzo[h]quinazolin-2-amine, 1-(3-(4-alkoxyphenyl)-7-methoxy-3,3a,4,5-tetrahydro-2H benzo[g]indazol-2-yl)ethanone, pyrazole and 2,6-diarylpyridine derivatives have been synthesized in good yields by an efficient methodology. The synthesized compounds (4-23) were evaluated for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. Compounds 6a, 6c, 8a, 19a and 19e exhibited significant anti-tubercular activity at MIC values 50, 100, 50, 25 and 100μM concentration. In vitro cytotoxicity data using THP-1 cells indicated that most active compound 19a is safe as its MIC value is much lower than the cytotoxic value.

Synthesis and biological evaluation of substituted 4,6-diarylpyrimidines and 3,5-diphenyl-4,5-dihydro-1H-pyrazoles as anti-tubercular agents

Various substituted 4,6-diarylpyrimidin-2-amine (4), 4,6-diaryl-2-(heteroaryl)pyrimidine (6) and 1-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)ethanone (7) derivatives were synthesized in good yields using simple methodology. The synthesized compounds (4-7) were evaluated for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. Compounds 4a, 6b, 7b, and 7c exhibited significant anti-tubercular activity at MIC values 25, 25, 12.5 and 12.5 μM concentration. In vitro cytotoxicity data using non cancerous hepatic monocytes (THP-1) cells indicated that most active compounds 7b and 7c were safe as their MIC values were much lower than their cytotoxic values.

A regioselective synthesis of 2,6-diarylpyridines

A regioselective synthesis of 2,6-diarylpyridines through base (sodium hydroxide in DMSO) catalyzed ring transformation of suitably functionalized 2H-pyran-2-ones with benzamide has been delineated. However, similar reaction of 2H-pyran-2-ones with benzamide using sodium hydroxide in absolute ethanol yielded highly congested delta keto esters with an active methylene centre, instead of 2,6-diarylpyridines.

Synthesis and evaluation of 2-heteroaryl and 2,3-diheteroaryl-1,4-naphthoquinones that potently induce apoptosis in cancer cells

This article describes the preparation of 2-heteroaryl and 2,3-diheteroaryl-1,4-naphthoquinones by an environmentally benign short synthetic route with the goal of finding 1,4-naphthoquinone derivatives that induce apoptosis in cancer cells. We have identified three most active naphthoquinones 10, 12 and 15 that potently induce apoptosis in human cervical carcinoma (HeLa) cells. One of these three compounds perturbed both microtubule and actin filaments.

Borontribromide-mediated C–C bond formation in cyclic ketones: a transition metal free approach

Borontribromide (BBr3) is a well-known demethylating agent. The current investigation was focused on a new application of borontribromide as a C–C bond forming agent in cyclic ketones. In this study, borontribromide mediated C–C bond formation reactions of tetralones, chromenone, thiochromenone and indanones were explored. A methoxy group containing ketones showed selective C–C bond formation reaction instead of demethylation of the methoxy group. MM2 steric energy calculations for the final products showed that the reaction favored the formation of exo- or endo-cyclic double bond containing products, depending upon their low MM2 steric energy in a specific frame structure, as observed in X-ray crystallography. A comprehensive crystallographic and pi-stacking analysis of product 10a demonstrated the formation of 10a as an enantiomeric mixture, and its centre of inversion was stabilized by a set of three unique pi–pi interactions.

Synthesis, photophysical and anticancer study of D-ring extended estrone analogues

A concise route for the highly substituted ring extended estrone derivatives has been established. This protocol involves very simple, facile and one step ring transformation and cyclization process. The preliminary absorption, emission spectroscopic and biological studies of these compounds revealed the possible use of such prototypes in cancer chemotherapy as fluorescence probes.

A convenient synthesis of pyrimidinone and pyrimidine containing bisheteroarenes and analogs

The synthesis of pyrimidinone containing bisheteroarenes (3) and related analogs (9 and 10) by the reaction of active methylenes or substituted methyl acrylate with nitrogen containing precursors viz. amidines, or thiourea in water as well as other organic solvents was studied. Synthesized compounds have further been explored for the synthesis of diversified pyrimidines 4, 6–8, 11, 12 and 14 through a sequential approach.

Choline chloride as an efficient catalyst for the synthesis of styryl-pyrazoles

ABSTRACT An efficient and green methodology for syntheses of various styryl-pyrazoles (3) from the reaction of 2-(5-phenyl-1H-pyrazol-3-yl)acetonitriles (1) with substituted benzaldehydes (2) by the use of biodegradable, nonhazardous, naturally occurring, and inexpensive choline chloride and NaOH under an environmentally benign medium has been described. GRAPHICAL ABSTRACT

Synthesis of 4-phenyl-5,6-dihydrobenzo[h]quinazolines and their evaluation as growth inhibitors of carcinoma cells

The synthesis of various benzo[h]quinazoline analogs (4a–f, 6a–d, 8a and 8b) was accomplished through the reaction of chalcone with guanidine. The synthesized compounds (4a–f, 6a–d, 8a and 8b) were screened for their anticancer potential against different cancer cells viz MCF-7, DLD1, A549, DU145 & FaDu cell lines. Compounds 4a, 6a–d & 8b showed significant anticancer activity in these cancer cell lines with a range of IC50 values of 1.5–12.99 μM. A functional study of promising molecule 6d at 7 μM (at the IC50 value) over 24 and 48 h showed that it possesses anticancer activity through triggering apoptosis. In a tubulin polymerization assay, 6d effectively inhibited tubulin polymerization with an IC50 of 2.27 μM. In silico docking studies of 6d revealed that 6d has good affinity with an estrogen receptor as well as a tubulin protein on its β-sheet of the colchicines binding site.