Isolation of isoxanthanol and synthesis of novel derivatives as potential cytotoxic agents

Abstract: Novel synthetic derivatives of sesquiterpene lactone isoxanthanol (1) have been prepared and bioevaluated against four human cancer cell lines viz. T98G (glioblastoma), A431 (epidermoid carcinoma), NCI-H322 (bronchioloalveolar carcinoma), and A549 (lung adeno carcinoma) for their cytotoxic potential using paclitaxel as the standard. This has resulted in the identification of potent molecules displaying IC₅₀ 1.9 and 5.0 µM, respectively against the A549 cancer cell line. The study has resulted in the identification of potential cytotoxic activity of the analog (compound 10) bearing electron donating aryl alkenoic substituent. Furthermore, the induction of cell death has been assessed for the most active compound (10) using flow cytometric method and sub-G1 cell population determination by propidium iodide staining. The concentration dependent inhibitory effect of 10 on the A549 cells ability did not reproduce and form colonies at 20 µM concentration. Graphical Abstract: Synthesis of isoxanthanol derivatives and their cytotoxic study resulted in identification of potential cytotoxic agents. Compound 10, one of its aryl alkenoic substituent showed potency against NCI-H322 (bronchioloalveolar carcinoma), and A549 (lung adeno carcinoma) cell lines. [InlineMediaObject not available: see fulltext.].