Novel Papaverine Metal Complexes with Potential Anticancer Activities

Abstract

Cancer is one of the leading causes of death worldwide. Although several potential therapeutic agents have been developed to efficiently treat cancer, some side effects can occur simultaneously. Papaverine, a non-narcotic opium alkaloid, is a potential anticancer drug that showed selective antitumor activity in various tumor cells. Recent studies have demonstrated that metal complexes improve the biological activity of the parent bioactive ligands. Based on those facts, herein we describe the synthesis of novel papaverine-vanadium(III), ruthenium(III) and gold(III) metal complexes aiming at enhancing the biological activity of papaverine drug. The structures of the synthesized complexes were characterized by various spectroscopic methods (IR, UV-Vis, NMR, TGA, XRD, SEM). The anticancer activity of synthesized metal complexes was evaluated in vitro against two types of cancer cell lines: human breast cancer MCF-7 cells and hepatocellular carcinoma HepG-2 cells. The results revealed that papaverine-Au(III) complex, among the synthesized complexes, possess potential antimicrobial and anticancer activities. Interestingly, the anticancer activity of papaverine-Au(III) complex against the examined cancer cell lines was higher than that of the papaverine alone, which indicates that Au-metal complexation improved the anticancer activity of the parent drug. Additionally, the Au complex showed anticancer activity against the breast cancer MCF-7 cells better than that of cisplatin. The biocompatibility experiments showed that Au complex is less toxic than the papaverine drug alone with IC₅₀ ≈ 111 µg/mL. These results indicate that papaverine-Au(III) complex is a promising anticancer complex-drug which would make it a suitable candidate for further in vivo investigations.

Keywords: X-ray structure; antibacterial; anticancer; bioactive metal complex; nanostructure; papaverine; pharmacological application.

Figure 1

Chemical structure of papaverine drug.

Figure 2

SEM of papaverine HCl (a) in complex with V(III) (b), Ru(III) (c) and Au(III) (d).

Figure 3

Proposed structure of M(III)–papaverine complex, where M = V(III), Ru(III) or Au(III).