Chem-bioinformatics and in vitro approaches for candidate optimization: a case study of NSC745689 as a promising antitumor agent

The benzothiazole scaffold has been reported to have antitumor activity in tumor-sensitive cell lines by proposed mechanism of CYP1A1 induction. CYP1A1 has been shown to participate in metabolism of benzothiazole scaffold to its reactive metabolites. CYP1A1 has also been proposed as drug target for anti-cancer chemotherapy for its differential and selective overexpression in tumor cells. Herein, we have reported NSC745689 from the series of new pyrimidobenzothiazoles (NSC745689) for its promising antitumor activity against non-small cell lung cancer cell line in National Cancer Institute (NCI) 60 human cancer cell line screen. We confirmed CYP1A1 specificity for NSC745689 by ethoxyresorufin-O-dethylase (EROD) assay. Furthermore, we investigated the metabolism of NSC745689 using MetaSite software and quantum mechanical study. The necessary structural changes in NSC745689 scaffold to potentiate its CYP1A1 binding and antitumor activity were suggested using molecular docking and molecular dynamics analysis.     

Phytochemical screening and evaluation of in vitro antioxidant and antimicrobial activities of the indigenous medicinal plant Albizia odoratissima

Context: Albizia odoratissima (L. f.) Benth has been used in Indian folk medicine to treat numerous inflammatory pathologies, such as leprosy, ulcers, burns and asthma.

Objective: To evaluate the antioxidant and antimicrobial properties of A. odoratissima.

Materials and methods: Dried leaves of A. odoratissima were extracted in organic solvents (hexane, chloroform, ethyl acetate, and methanol). The total phenolic content (TPC) and total flavonoid content (TFC) were determined using the Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. The antioxidant activity was examined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H₂O₂), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS), and ferric reducing antioxidant power (FRAP) assays. The antibacterial activity was examined using minimum inhibitory concentration (MIC) and the minimum bacterial concentration (MBC), determined by broth microdilution method against Gram-negative bacteria (Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Proteus vulgaris) and Gram-positive bacterium (Staphylococcus aureus).

Results: The TPC ranged from 4.40?±?1.06 to 1166.66?±?31.85?mg GAE/g of dry weight (DW), and the TFC ranged from 48.35?±?3.62 to 109.74?±?1.84?mg QE/g of DW. The IC₅₀ values of the ethyl acetate extract for DPPH, ABTS, and H₂O₂ were 10.96?±?0.40, 4.35?±?0.07, and 163.82?±?1.52?μg/mL, respectively. Both methanol and ethyl acetate extracts demonstrated effective antibacterial activity with MICs and MBCs values ranging 136–546?μg/mL and 273–1093?μg/mL, respectively, against the tested pathogenic species.

Conclusions: The leaves of A. odoratissima showed potent free radical scavenging property and antimicrobial activity.