Biological Activities and Docking Studies on Novel Bis 1,4-DHPS Linked to Arene Core via Ether or Ester Linkage

Background: Novel bis(1,4-dihydropyridine) derivatives linked to arene core via ester 5- 7 as well as ether linkages 10-12 were prepared, and their structures were confirmed by several spectral tools. They were evaluated as anticancer agents on A549 and MCF7 cell lines by SRB assay and as antibacterial agents on two gram-positive and two gram-negative bacterial strains by disc diffusion method. Methods: SRB assay shows that the novel compounds are more effective against lung carcinoma than human breast cancer. Compound 7 was found to be the most active compound toward A549 cell line with an IC50 value (30.7μM), while compound 12 showed great efficiency against MCF7 cell line recording an IC50 value (46.3μM). The computational studies enabled us to understand the mechanism of action of these compounds. Compound 7 was chosen for molecular docking studies on xIAP and cIAP1 proteins using MOE-2009.10 software, and the results obtained show that compound 7 bound to xIAP and cIAP1 with good energy score (S = -22.0356 Kcal/mol and -21.3381Kcal/mol), respectively. Results: With respect to the antibacterial activity, compound 12 exhibited great efficiency against the bacterial strains and hence it was used in the docking study on β-ketoacyl-ACPsynthaseIII (fabH). Conclusion: The results showed good interaction of compound 12 with fabH (with energy score S = -22.8975 kcal/mol).