Formation of morpholine-acetamide derivatives as potent anti-tumor drug candidates: Pharmacological evaluation and molecular docking studies

Abstract

Heterocyclic amines and acetamide derivatives are known for their chemotherapeutic potential. Hence, in the present study, morpholine was taken as a principal product and novel morpholine derivatives were designed, formulated, characterized, and screened for the mechanism of inhibition of carbonic anhydrase and their anticancer potential. In addition, in vitro inhibition of hypoxia-inducible factor-1 (HIF-1) protein was also investigated. Results revealed that compounds 1c, 1d, and 1h possessed significant inhibitory activities against carbonic anhydrase with IC50 of 8.80, 11.13, and 8.12 μM, respectively. Interestingly, the carbonic anhydrase inhibitory activity of compound 1h was comparable with that of standard acetazolamide (IC50 7.51 μM). The compounds 1h and 1i significantly inhibited the proliferation of ovarian cancer cell line ID8 with IC50 of 9.40, and 11.2 μM, respectively while the standard cisplatin exhibited an IC50 8.50 μM. In addition, compounds 1c, 1b, 1h and 1i also exhibited significant inhibitory effects on HIF-1α. In conclusion, we report first time the biological potential of morpholine based compounds against ovarian cancer and HIF-1α that may serve as lead molecules for drug discovery.

Keywords

• Heterocyclic amines
• Morpholine based compounds
• Anti-tumor activity
• MTT (3-[4,5-dimethylthiazole-2-yl]-2,5 diphenyl tetrazolium bromide) assay
• Carbonic anhydrase inhibition
• HIF-1α