Molecular docking and in vitro anticancer studies of silver(I)- N-heterocyclic carbene complexes

Mitat Akkoç; Siraj Khan; Hande Yüce; Neşe Başak Türkmen; Şeyma Yaşar; Sedat Yaşar; İsmail Özdemir

doi:10.1016/j.heliyon.2022.e10133

Molecular docking and in vitro anticancer studies of silver(I)- N-heterocyclic carbene complexes

Heliyon. 2022 Aug 6;8(8):e10133. doi: 10.1016/j.heliyon.2022.e10133. eCollection 2022 Aug.

Authors

Mitat Akkoç¹, Siraj Khan², Hande Yüce³, Neşe Başak Türkmen³, Şeyma Yaşar⁴, Sedat Yaşar⁵, İsmail Özdemir^{5

6}

Affiliations

¹ Malatya Turgut Özal University, Hekimhan Vocational College, Department of Property Protection and Security, Hekimhan, Malatya, Turkey.
² Quaid-i-Azam University, Faculty of Biological Sciences, Department of Pharmacy, Islamabad, 45320, Pakistan.
³ İnönü University, Faculty of Pharmacy, Department of pharmaceutical toxicology, 44280 Malatya, Turkey.
⁴ Inönü University, Faculty of Medicine, Department of Biostatistics and Medical Informatics, 44280 Malatya, Turkey.
⁵ İnönü University, Faculty of Science and Arts, Department of Chemistry, 44280 Malatya, Turkey.
⁶ İnönü University, Drug Application and Research Center, 44280 Malatya, Turkey.

Abstract

A series of symmetric and unsymmetrical benzimidazolium-based N-heterocyclic carbene (NHC) precursors (1a-i) and their silver complexes (2a-i) have been synthesized. The Ag(I)-NHC complexes were characterized by ¹H, ¹³C{¹H} NMR, FTIR, LC/MS-QTOF, and elemental analysis. Anticancer and cytotoxic activity of all Ag(I)-NHC complexes were tested against healthy fibroblast cell line (L929), breast cancer cell line (MCF-7), and neuroblastoma cell line (SH-SY5Y) by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4sulfophenyl)-2H-tetrazolium] assay. The 2b, 2c, 2e, 2g, 2h, and 2i complexes showed higher cytotoxicity than cisplatin against SH-SY5Y and MCF-7 and lower cytotoxic activity against L929 cell lines. Because of their high cytotoxic activity against cancer cells and low cytotoxicity against healthy fibroblast cell lines, the 2b, 2c, 2e, 2g, 2h, and 2i are expected to be new lead compounds. In addition, molecular docking studies were performed to explore the binding interactions of silver complexes with the enzyme to explore new anticancer compounds. Furthermore, ADME properties of all complexes were predicted to explore lead-like characteristics and may be a potential drug candidate for cancer treatment.

Keywords: Anticancer activity; Breast cancer cell line (MCF-7); Healthy fibroblast cell line (L929); Neuroblastoma cell line (SH-SY5Y); Silver-N-heterocyclic carbene.