Silver derivatives of multi-donor heterocyclic thioamides as antimicrobial/anticancer agents: unusual bio-activity against methicillin resistant S. aureus, S. epidermidis, and E. faecalis and human bone cancer MG63 cell line

Abstract

The basic aim of this study pertains to the synthesis of silver nitrate complexes and the study of their antimicrobial and anticancer bio-activity. A series of new silver(I) derivatives of N-substituted-imidazolidine-2-thiones (L-NR, R = Et, Prⁿ, Buⁿ, Ph), purine-6-thione (purSH₂), 2-thiouracil (tucH₂), pyrimidine-2-thione (pymSH) and pyridine-2-thione (pySH) of composition [Ag(S-L-NR)(PPh₃)₂(ONO₂)] {R = Et (1), Prⁿ (2), Buⁿ (3), Ph (4)}, [Ag₂(N,S-purSH₂)₂(μ-dppm)₂](NO₃)₂·2H₂O (5) (dppm = Ph₂P–CH₂–PPh₂), [Ag(L)(PPh₃)₂](NO₃) {L = N,S-purSH₂ (6); S-tucH₂ (7)}, [Ag(N,S-pymS)(PPh₃)₂](CH₃OH) (8), and [Ag(N,S-pyS)(PPh₃)₂] (9) have been synthesized and structurally characterized. These new and some previously reported complexes {[Ag₂(L-NH)₄(PPh₃)₂](NO₃)₂ (10), [Ag(L-NMe)₂(PPh₃)](NO₃) (11), and [Ag(S-bzimSH)₂(PPh₃)₂](OAc) (12), L-NH = 1,3-imidazolidine-2-thione; L-NMe = 1-methyl-3-imidazolidine-2-thione and bzimSH₂ = benzimidazoline-2-thione)} have shown moderate to high anti-microbial activity against Gram positive bacteria, namely methicillin resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (MTCC 740), and Gram negative bacteria, namely Staphylococcus epidermidis (MTCC 435), Enterococcus faecalis (MTCC 439), Shigella flexneri (MTCC 1457) and a yeast Candida albicans (MTCC 22). These complexes have also been found to be bio-safe as studied using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. The anti-tumor study of silver complexes against human osteosarcoma cell line (MG63) has shown IC₅₀ values in the range of 6–33 μM.