Synthesis and pharmacological activities of morpholine and coumarin derivatives / Muhammad Afifi Mohd Faridz

• Main Author: Mohd Faridz, Muhammad Afifi
• Format: Thesis
• Language: English
• Published: 2019
• Online Access: https://ir.uitm.edu.my/id/eprint/99571/1/99571.pdf; https://ir.uitm.edu.my/id/eprint/99571/

Plant-based natural products have played a major role in the development of new drug candidates. Organic synthesis has overcome the limitation of the compounds from natural sources, which provide and develop new pharmaceutical products. In order to explore new therapeutic synthetic compounds, the morpholine scaffold had found to be an outstanding pharmacophore in medicinal chemistry and number of molecules having morpholine skeleton are the clinically a drug. Seventeen novel derivatives of morpholine were synthesised by different arylhydrazides and 5-morpholinothiophene2-carbaldehyde. All synthesised compounds (83-99) were evaluated for their in-vitro anticancer potential against two human cancer cell lines, HepG2 and MCF7. Seventeen coumarin-based derivatives (101-117) were screened for a-glucosidase inhibitor activity and 3-formylcoumarin (118-134) analogues were screened for thymidine phosphorylase inhibition. All compounds showed a variable degree of inhibitions when compared to the standard inhibitors. Molecular docking studies were carried out to understand the binding interaction of active compounds. Analogues 95 had similar substantial inhibition effects towards HepG2 with IC50 value 6.76±3.12 //M, when compared with the standard doxorubicin (IC50 value 6.59±0.45 JUM); while compounds 87, 90 and 91 showed potent cytotoxicity against MCF7 with IC50 value 7.08±0.42 fiM, 1.26±0.34 JUM and 11.22±0.22 JUM respectively, when compared with the standard tamoxifen (IC5o=9.53±0.40 JUM). Coumarin-based derivatives, analogue 105 inhibition seems effective towards HepG2 and MCF7 with IC50 values 0.02±1.78 juM and 10.23±1.77