Synthesis of Compounds Derived Calkon As antimalarial compounds, anticancer and antimicrobial
ABSTRACT: Synthesis and antimalarial, anticancer, and antimicrobial activity test of methoxy-4'-amino chalcone derivatives have been conducted in this research. The prepared chalcone derivatives were designed as inhibitor of the interaction of PfFdPfFNR in the apicoplast of Plasmodium falciparum. As anticancer and antimicrobial agents, the synthesized compounds were designed as inhibitor of dihydropteroate synthase (DHPS), which plays a crucial role in the folic acid biosynthesis for cell proliferation. The chalcone derivatives were synthesized using Claisen-Schmidt reaction. Their structures were elucidated based on the spectroscopy evidences. Enzyme PfFd was isolated from E. coli JM105 (pTrs99a), whereas PfFNR was isolated from E. coli TG1 (pTrs99a). Inhibition of PfFNR-PfFd interaction activity of the prepared compounds was determined by Cyt-c assay. Anticancer activity test was examined by MTT assay using breast cancer cell line T47D, while the antimicrobial activity was tested by paper disc inhibition method using Eschericia coli ATCC 25923, Staphylococcus aureus ATCC 25922, and Candida albicans ATCC 10231. The yields of the desired compounds were in the range of 42-98%. The prepared compounds were able to inhibit the interaction of PfFd-PfFNR in range of 4.49 - 50%. Compound MT-3 exhibited the strongest inhibition activity. Based on docking experiment, the prepared compounds showed greater affinity to maize leafPfFNR than to PfFd. It was proved that electron flow during respiration proceeds from PfFNR to PfFd. The anticancer test showed that the IC50 values of the prepared compounds were in the range of 5.38 - 48.77 µg/mL, and MT-7 was the most potent. Amino group played an important role for anticancer activity, methoxy group played insignificant role, whereas bromo group decreased the anticancer activity. The antimicrobial test showed that MT-4 possessed good potential to be used as a wide spectrum antimicrobial agent. Docking experiment showed that the prepared compounds showed greater affinity to DHPS S. aureus than to E. coli, and it was assumed that they can act as a competitive inhibitor of hydroxymethylpterin pyrophosphate.
