Podcast by: Dr. Khushal Kapadiya

Authors: Dr. Mayank Pandya, Dr. Khushal Kapadiya

Journal Name: Letters in Drug Design & Discovery

Read the Article here: https://www.eurekaselect.com/189473/article

Article Abstract:

Background: The era of drug discovery suggested the designing of “hybrid drugs,” which acquired the recognition in the field of medicinal chemistry due to it’s influential role in preserving different health challenges.

Objective: A new series of chalcone derivatives 4a-4i, bearing isoxazole moieties, were designed and synthesized with microwave irradiation, which were biologically evaluated for their activity on NCI-60 cell-lines to check efficacy in anticytotoxic effect.

Methods: The required diverse acetophenone molecule was prepared by chloro-amine coupling using lansoprazole (lanso chloro) drug intermediate, i.e., 4-(2,2,2-trifluoroethoxy)-2-(chloromethyl)-3-methylpyridine engaged in the reaction with various aryl aldehydes (2a-2i) in the primary media gave fluoro contained chalcone (3a-3i). The desired isoxazoles (4a-4i) were synthesized by MW (microwave irradiation) based reaction using hydroxylamine for cyclization purposes.

Results: The espoused scheme resulted in good yields of a new set of isoxazole-chalcone conjugates with potent cytotoxic activity were found in compounds 4h and 4i against Leukemia RPMI-8226 (With GI50 Values ≈ -10 µg/ml) cancer cell line and Non-Small Cell Lung Cancer HOP-92 (With GI50 Values ≈ -25 µg/ml) cancer cell line.

Conclusion: The optimization of the reaction indicated that the MW based reaction progress was an efficient and timesaving process for the course of isoxazole synthesis. An anticancer study shows that compounds 4h demonstrated significant anti-cancer activity.

Keywords: Isoxazoles, Leukemic Cancer, Non-small-cell Lung cancer, Microwave assisted synthesis, Chalcones, HOP-92, RPMI-8226