Isatin-based oxime ethers as anticancer agents against human colorectal carcinoma.

Authors

Shashikala Mariswamy Rajesh, Priyadarshini A N, Vinay Kumar D C, Sudhanva Muddenahalli Srinivasa, Toreshettahally R Swaroop, Rajaghatta N Suresh, Shobith Rangappa, Kanchugarakoppal S Rangappa

Published in

Naunyn-Schmiedeberg's archives of pharmacology. Jul 01, 2026. Epub Jul 01, 2026.

Abstract

Colorectal cancer is one of the leading causes of cancer-related deaths and ranks third among them. Our efforts to develop new anticancer agents to treat this disease resulted in the synthesis of new isatin-based oxime ethers. The cytotoxic effects of these compounds against HCT116 were analyzed using MTT and Trypan Blue dye exclusion assays. A compound 10d has emerged as a lead compound with IC₅₀ value of 22.31 ± 1.23 µM. Even though this molecule is two-fold less active than reference drug 5-fluorouracil (5-FU), the pharmacophore of the compound 10d would be considered for future derivatisation as a notable anticancer agent, due to its safety profile against normal cell line HEK. The anticancer effect of compound 10d against colon cancer cells was demonstrated by cell shrinkage and detachment observed under bright-field microscopy. Furthermore, Hoechst/propidium iodide (PI) staining and acridine orange (AO)/PI staining analysis confirmed the induction of cell death. Treatment with compound 10d restrains colony formation ability and mitigates the migratory potential of colon cancer cells as observed by both foci formation and migration assay. Finally, we elucidated the possible mode of action of the lead molecule by in-silico analysis using molecular docking studies. Results unveiled that the lead compound exhibits anticancer potential probably by targeting Human Tankyrase-2 and Bruton's tyrosine kinase with high docking scores, as evident by in-silico modelling. The binding affinity of synthetic compounds against the protein targets 5BXU and 7LTZ was assessed by molecular docking experiments. The compound 10d demonstrated the greatest affinity for both targets (- 8.8 and - 7.9 kcal/mol, respectively), whereas other compounds showed favourable binding energies. These findings suggest that compound 10d may serve as a promising lead for further biological evaluation.

PMID:
42384169
Bibliographic data and abstract were imported from PubMed on 01 Jul 2026.

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