Shilpi Singh, P. Kumari, Yusuf Hussain
Jul 9, 2020
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Current topics in medicinal chemistry
Abstract
BACKGROUND Since centuries plant-based compounds are known for the treatment of cancer in both traditional and contemporary medicine. The problems like target non-specificity and toxicity are well-known regarding anticancer drugs. Therefore, target specific search of novel entities is constant. Isothymusin is a dimethoxy, trihydroxy flavone present in plants like Ocimum sanctum, Limnophilla geoffrayi. There are limited reports available on the anticancer potential of isothymusin. OBJECTIVES The efficacy of isothymusin on redox status, cell cytotoxicity, and targets involved in the promotion and progression of the cancer cells have been investigated. METHODS Antiproliferative efficacy was evaluated by MTT, Neutral Red Uptake, and Sulforhodamine-B assays. The spectrophotometric methods were adopted to study the effect against selected targets. Redox activity was assessed by in vitro antioxidant assays and the interaction study, ADMET profiling, and toxicity assessments were done in silico. RESULTS Isothymusin scavenges the radicals, i.e., DPPH and nitric oxide with moderate ferric reducing potential. It affected the proliferation of leukemia, colon, skin, and breast cancer cell lines by more than 50% but moderately affected prostate, kidney, lung, hepatic, and breast adenocarcinoma (up to 48%). Isothymusin inhibited the enzymes associated with the promotion stage of cancer, including cycloxygenase-2 and lipoxygenase-5. Additionally, it also inhibited the activity of proliferation markers like cathepsin-D, dihydrofolate reductase, hyaluronidase, and ornithine-decarboxylase. Besides, in silico studies supported the in vitro enzyme inhibition assays outcome. Toxicity studies showed promising results of chemical descriptors and non-skin-irritant, moderate ocular-irritancy, and in vitro Ames test confirmed non-mutagenic nature. CONCLUSION Isothymusin showed antiproliferative and radical scavenging activity and could be taken up as a lead for further derivatization to prepare better analogues with improved anticancer potential.