Thaigarajan Parumasivam

Design, characterization, in vitro antibacterial, antitubercular evaluation and structure–activity relationships of new hydrazinyl thiazolyl coumarin derivatives

Herein, we describe the synthesis of 11new thiazolyl coumarin derivatives and evaluation of their potential role as antibacterial and antituberculosis agents. The structures of the synthesized compounds were established by extensive spectroscopic studies (Fourier transform infrared spectroscopy, 1H-nuclear magnetic resonance, 13C-nuclear magnetic resonance, 2D-nuclear magnetic resonance and liquid chromatography–mass spectrometry) and elemental analysis. All synthesized compounds were assayed for their in vitro antibacterial activity against a few gram positive and gram negative bacteria and antituberculosis activity against Mycobacterium tuberculosis H37Rv ATCC 25618 by using colorimetric microdilution assay method. Nine derivatives showed moderate anti-bacterial and anti-tuberculosis activities against all the tested strains. The highest activity against all the pathogens including Mycobacterium tuberculosis was observed by compound 7c with MIC values ranging between 31.25–62.5 μg/mL, indicating that coumarin skeleton could indeed provide useful scaffold for the development of new anti-microbial drugs.

Synthesis, X-ray crystallographic study, pharmacology and docking of hydrazinyl thiazolyl coumarins as dengue virus NS2B/NS3 serine protease inhibitors

A series of total twenty-one thiazole-coumarin derivatives 7a-u, linked via hydrazine linkage were synthesized through Hantzsch cyclisation. Out of twenty-one derivatives, fourteen derivatives viz. 7b-d, 7g, 7i-k, 7n and 7p-u are the novel derivatives. The structures of the synthesized compounds were established by extensive spectroscopic studies (FTIR, 1H NMR, 13C NMR, 2D NMR, LC-MS) and elemental analysis. The structure of (E)-6-methoxy-3-(1-(2-(4-p-tolylthiazol-2-yl)hydrazono)ethyl)-2H-chromen-2-one (7d) was unambiguously confirmed by X-ray crystallography analysis. Hybrid molecules were evaluated for their potential as anti-tubercular agents against Mycobacterium tuberculosis H37Rv ATCC 25618, and anti-bacterial agents against Eschericia coli, Enterobacter aerogenes, Salmonella typhi, Streptococcus pneumoniae and Staphylococcus aureus. All the compounds displayed considerable potency against all the pathogens with MIC values ranging from 31.25 to 250 μg/mL, therein compounds 7i, 7j, 7k, 7q and 7t displayed superior inhibitory activities compared to standard drugs streptomycin, kanamycin, vancomycin and isoniazid. Molecular docking studies were performed to check the potential as dengue virus NS2B/NS3 serine protease inhibitors, by comparing to standards 4-hydroxypanduratin, panduratin and ethyl 3-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy)propanoate with DS of −3.379, −3.189 and −3.381, respectively. All the compounds were found to exhibit potency against the DENV virus. In particular, compound 7c (DS –5.141) and 7l (DS –3.894) were found to be even better than the standards followed by compounds 7j (DS –3.113) and 7q (DS –3.561).

The Effectcs of Ageratum conyzoides Fractions on the Growth Dynamics and Cellular Morphogenesis of

Ageratum conyzoides is a common weed locally known as rumput tahi ayam, which thrives in the proximity of habitation in any soil, in waste lands and ruined sites. In traditional Malaysian medicine, A. conyzoides is used to treat a variety of ailments including symptoms of tuberculosis (TB). In this study, we investigated the anti-TB activity of different fractions of this plant and their effects on the growth dynamics and cellular morphogenesis of Mycobacterium tuberculosis H37Rv ATCC 25618 to validate its traditional use. The methanol, n-hexane, chloroform, ethyl acetate, n-butanol, and aqueous fractions of A. conyzoides (whole plant) were screened for their in vitro anti-TB activity using a colorimetric tetrazolium microplate assay against the tubercle bacilli. The effects of the most active fractions on the growth of the mycobacteria was studied over a 7-day exposure in Middlebrook 7H9 broth and the colony counts were evaluated from growth on Middlebrook 7H10 agar plates after 21 days incubation. The effects of the fractions on the cellular morphogenesis of M. tuberculosis was observed under scanning electron microscope (SEM). All the six fractions exhibited activity with MICs in the range of 1600-100 µg/ml. The highest activity was exhibited by n-hexane with MIC/MBC values of 100/100 µg/ml followed by chloroform with MIC/MBC values of 100/200 µg/ml. The growth dynamics of the mycobacteria were followed based on the percentage of initial colony counts on day 0 as compared to the negative (isoniazid) and positive controls. The results indicated that the n-hexane and chloroform fractions exerted immediate cidal effects on M. tuberculosis as shown by a sharp decrease of more than 90% of the initial colony count on day 0 after only one day exposure. By the end of the study period less than 1% of the initial cell population remained viable. The results of SEM observation demonstrated striking effects of the fractions on the cellular morphology of M. tuberculosis compared to the control cells with clear evidences of cellular damage. The outcome of this study gives a scientific basis to the traditional use of A. conyzoides for symptoms of TB and this plant could be a potential source of anti-TB compounds worthy of further investigation.