Examination of antitumor potential of some acylpyruvates, interaction with DNA and binding properties with transport protein

Abstract

With the idea of finding a new antitumor drug with better or similar to one already used in clinical practice today, we tested a small series of acylpyruvate on a cisplatin-resistant MDA-MB-231 tumor cell line. All but one of the compounds in the series showed better cytotoxicity than cisplatin. In addition, compounds that showed good cytotoxicity on the MDA-MB-231 cell line were also tested on the normal MRC-5 cell line to determine its selectivity. All tested compounds showed better selectivity in the tested cell line than cisplatin. Good selectivity is one of the crucial factors for a new antitumor drug candidate. By examining the interactions with DNA, we concluded that our compounds interact with the DNA molecule through intercalation. On the other hand, by examining the binding mode of acylpyruvate to a transport protein, it was found that these compounds interact with the tested protein, indicating that the tested compound can be transported and adequately distributed to cells. A molecular docking study was performed to examine in more detail the sites and mode of binding to DNA and serum albumin molecules. In conclusion, all results indicate the great potential for the prospective application of these compounds in clinical practice in the future.