Novel Papaverine Metal Complexes with Potential Anticancer Activities

• Published in: Molecules (Basel, Switzerland) Switzerland), 2020-11, Vol.25 (22), p.5447
• Main Authors: Gaber, Ahmed, Alsanie, Walaa F, Kumar, Deo Nandan, Refat, Moamen S, Saied, Essa M
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; antibacterial; anticancer; Antiinfectives and antibacterials; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; bioactive metal complex; Biocompatibility; Biological activity; Breast cancer; Cancer therapies; Cell Line, Tumor; Cell Survival - drug effects; Chemical compounds; Chemistry Techniques, Synthetic; Cisplatin; Coordination Complexes - chemistry; Drugs; FDA approval; Gold; Hepatocellular carcinoma; Humans; In vivo methods and tests; Investigations; Ligands; Magnetic Resonance Spectroscopy; Metal complexes; Metals; Microbial Sensitivity Tests; Molecular Structure; nanostructure; Nanostructures - chemistry; Nanostructures - ultrastructure; NMR; Nuclear magnetic resonance; papaverine; Papaverine - chemistry; Pharmacology; Pulmonary arteries; Ruthenium; Side effects; Structure-Activity Relationship; Tumor cell lines; Tumor cells; Vanadium; X-ray structure
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25225447

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 IC ≈ 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.