Pathi Suman

Synthesis, structure–activity relationship of novel substituted 4H-chromen-1,2,3,4-tetrahydropyrimidine-5-carboxylates as potential anti-mycobacterial and anticancer agents

Series of 4H-chromen-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives 7a-7zb, 8a-8d and 9a-9d were synthesized and screened for their in vitro anti-mycobacterial activity against Mycobacterium tuberculosis H(37)Rv (MTB) and cytotoxicity against three human cancer cell lines including A549, SK-N-SH and HeLa. The results indicate that six compounds are more potent and 7za is most effective anti-mycobacterial derivative compared to the standard drugs Ethambutol and Ciprofloxacin. However, 12 compounds exhibited cytotoxicity against human neuroblastoma cell line; amongst them the compound 7v is most effective compared to the standard drug Doxorubicin. This is the first report assigning in vitro anti-mycobacterial, anticancer and structure-activity relationship for this new class of 4H-chromen-1,2,3,4-tetrahydropyrimidine-5-carboxylates.

Synthesis and structure–activity relationships of pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles as potent inhibitors of tubulin polymerization

Three series of compounds; pyridinyl-1H-1,2,3-triazoles, pyridinyl-1H-1,2,3-triazolylisoxazoles and pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles with TMP moiety were designed, synthesized and screened for their anti-cancer and anti-tubulin properties. By sequentially designing three series of compounds comprising of dihydroisoxazole in the linker, a small substituent like chlorine on one side (R(1)) and aromatic group (R) on the pyridine ring, we have optimized the anti-cancer as well as anti-tubulin activity. Pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles 28b and 28c were found to be potent anti-cancer agents against all the cell lines tested with a concomitant accumulation of cells in the G2/M phase of the cell cycle. Molecular modeling suggests that the trimethoxyphenyl ring in 28b and 28c occupies the cholchicine binding domain of β-tubulin, whereas, the dihydroisoxazole extends towards the interface of α,β-tubulin.

Synthesis and anti-mycobacterial activity of 2-chloronicotinaldehydes based novel 1H-1,2, 3-triazolylbenzohydrazides

1H-1,2,3-Triazolylbenzohydrazides (6a-h and 11a-l) were synthesized from 2-chloronicotinaldehydes and evaluated for anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv strain (ATCC-27294). Seven compounds 6b, 6e,f, 11d, 11h, 11j and 11l displayed potent anti-mycobacterial activity (MIC 2.8-6.2 μM). Potent anti-mycobacterial compounds were chosen for cytotoxicity studies by MTT protein assay against normal cell lines (PBMC and Raw 264.7) and shown low cytotoxicity. This is the first Letter assigning anti-mycobacterial activity, cytotoxicity and structure activity relationship for 1H-1,2,3-triazolylbenzohydrazides.

Facile construction of novel heterocyclic compounds: three-component, one-pot synthesis of 2-hydroxybenzoyl-1,2-dihydropyridine-3-carboxylates, ketones, pyridone-3-carboxylates and benzopyrido-1,3-oxazole-4-carboxylates

A facile method has been developed for the preparation of novel heterocyclic compounds by the reaction of 3-formylchromones, benzylamines, and 2-aminophenols with 3-oxobutanoates. 3-Oxobutanoates bearing trifluoro or trichloro substituents and trifluoro containing 1,3-diketones facilitated the reaction. The reaction proceeds via a Schiff base mediated Michael addition followed by the selective addition of enamine to the carbonyl group adjacent to the trihalo group due to a strong electron withdrawing effect. The present three-component, one-pot protocol provided heterocyclic compounds without a catalyst.

Condensation of Ortho-phenylenediamines and Phenylhydrazines with Ethyl 4-Chloro-3-oxobutanoate: A Facile Approach for the Synthesis of Substituted 1H-Benzimidazoles, Pyrazolones, and Pyrazoles

Abstract Substituted 1H-benzimidazoles, pyrazolones, and pyrazoles have been synthesized by the condensation of ortho-phenylenediamines and phenylhydrazines, respectively, with ethyl 4-chloro-3-oxobutanoate in good yields. The present approach is novel, straightforward, and being reported for the first time with ethyl 4-chloro-3-oxobutanoate. GRAPHICAL ABSTRACT

Anti-proliferative, structure–activity relationship of pyridinylchalcones and chromanones

A series of pyridinylchalcones 3a–q, chromanones 4a–q were prepared and screened for their in vitro anti-proliferative activity against four human cancer cell lines viz., cervical (HeLa), lung adenocarcinoma (A549), prostate (DU-145) and breast (MDA-MB-231). Pyridinylchalcones 3a-q and chromanones 4a-q exhibited IC50 values in the range of 5.9–289 µM. Compound 3e exhibited an IC50 of 5.9 µM and also increased caspase-3 activity to ~ 2.7-fold at 10 µM concentration in HeLa cell line. Cell cycle analysis further confirmed the apoptotic effects of 3e due to a substantial increase in cells arrested at sub-G1 phase of cell cycle. Further, the loss of mitochondrial membrane potential in 3e treated cells indicates that the intrinsic pathway of apoptosis might be responsible in 3e induced apoptosis.Graphical AbstractPyridinylchalcones, chromanones were screened for their in vitro anti-proliferative activity against four human cancer cell lines by the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay method. Pyridinylchalcones and chromanones exhibited IC50 values in the range of 5.9–289 µM. Compound 3e exhibited an IC50 of 5.9 µM and also increased caspase-3 activity to ~2.7-fold at 10 µM concentration in HeLa cell line