Shasank S. Swain

Antibacterial activity, computational analysis and host toxicity study of thymol-sulfonamide conjugates

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecalis (VRE) are notorious pathogenic multidrug resistant (MDR) bacteria in both hospital and community sectors, and today the first antibacterial drug sulfamethoxazole is ineffective. The monoterpene phenol, thymol was conjugated with seven sulfa drug derivatives individually, adopting the dye-azo synthesis protocol, and conjugates were characterized using spectral analysis techniques such as, UV, FTIR, MS, HPLC, 1H NMR, 13C NMR and SEM. Conjugates were assessed for antibacterial activity in vitro and in silico; the zone of inhibition, MIC and MBC values of each conjugate were determined against isolated MRSA and VRE strains from clinical samples. As 3-dimentional structures of dihydropteroate synthases (DHPSs) of targeted bacteria are not available in protein database, homology models of DHPS enzymes of both bacteria were generated and validated by Ramachandran plots. Seven conjugates were used as ligands in molecular docking against MRSA-DHPS and VRE-DHPS. Additionally bioinformatics tools, PASS prediction, Lipinski rules of five, computational LD50 value, toxicity class, HOMO, LUMO and EPS plots were carried out to assess standard drug-likeliness properties of conjugates. Zone size inhibition of the conjugate, 4b (thymol+sulfadiazine) against MRSA and VRE strains on agar plates were 20 and 40μg/mL as the lowest MIC and MBC values, respectively; while the reference antibiotic ampicillin had the lowest MIC and MBC values at 80 to 180μg/mL. In vitro host-toxicity testing was carried out with cultured human-lymphocytes from umbilical cord blood, and 4b was broadly non-toxic to human cells at 15,000mg/L. Thus, 4b could be promoted a newer antibacterial, against gruesome MDR bacteria.

Anticancer compounds from cyanobacterium Lyngbya species: a review

The use of synthetic anticancer drugs and other methods followed in cancer therapy have several side effects; and ineffective methods or drugs give a way to the emergence of drug resistant cancer cells, with the intrinsic metastasis as the aftermath. Anticancer efficacy of many cyanobacterial compounds has been claimed in literature. This review considers 144 compounds isolated and characterized from seven species of the non-nitrogen fixing filamentous cyanobacterium Lyngbya, as the source of antineoplastic agents, which have been screened primarily with cancer cell lines. Structure and information of Lyngbya compounds were retrieved from databases, PubChem, ChemSpider and ChEBI. Information and clinical status of Lyngbya compounds are summarized, and those might be the future anticancer drugs for drug-resistant cancer cells even, as complementary/adduct drugs, if pursued thoroughly in pharmacology and pharmaceutics.

Synthesis of novel thymol derivatives against MRSA and ESBL producing pathogenic bacteria.

Abstract Twelve substituted aryl-azo-thymol derivatives (4a to 4 l) were synthesized and characterized by several spectral techniques such as, FTIR, UV-vis, proton NMR, Mass spectrometry and elemental analysis. Antimicrobial activities were evaluated by agar-well diffusion method against isolated MRSA, ESBL-producing pathogenic bacteria and antifungal resistant fungi, in vitro. In addition, drug likeness properties of derivatives were assessed through bioinformatic tools such as, PASS prediction, molecular docking and Lipinski rules of five, along with determination of toxic nature and LD50 values. Among 12 derivatives, 4a, 4b, 4c, 4 g, 4i, 4j and 4 k had significant antibacterial and antifungal activities with minimum inhibitory concentration values, 40 to 80 μg/ml. Moreover, the docking scores of derivatives were −8.27 to −11.44 kcal/mol, against 4 bacterial targets and −9.45 to −12.49 kcal/mol against 2 fungal targets. Thus, from in vitro and in silico studies, thymol derivatives had control of MRSA, ESBL-producing bacteria and antifungal resistant fungi.