Evaluation of substituent bioactivity and anion impact of linear and T-shaped silver(i) pyridinyl complexes as potential antiproliferative, antioxidant, antimicrobial agents and DNA- and BSA-binders

Abstract

Transition metal-based drugs have shown to be good therapeutic agents and in the same effort, our work has continued the search for even better ones. Four pyridinyl Schiff bases (E_a–E_d) and their silver(I) nitrate, perchlorate, and triflate complexes (1–12) were synthesized and characterized by elemental analysis, FT-IR, ESI-MS, UV-Vis, ¹H and ¹³C NMR spectroscopy, and single-crystal X-ray diffraction. The analysis confirmed a linear geometry around the Ag(I) center for all complexes in the solution, and a T-shaped geometry for complexes 10 and 12 in the solid-state. The newly synthesized compounds were screened for their in vitro anticancer, antioxidant, and antimicrobial activities. In addition, their interactions with calf thymus-DNA (CT-DNA) and bovine serum albumin (BSA) were also studied. Complexes possessing either methyl substituent or the thiazole moiety showed better in vitro antimicrobial activity against the tested bacteria, especially against Gram-negative bacteria. The anions ClO₄⁻ and CF₃SO₃⁻ were observed to have some influence on the antimicrobial activities also. Effective scavenging activity in FRAP assay was observed for complexes with OH⁻ or F⁻ as substituents with IC₅₀ values between 0.79 and 2.02 mg mL⁻¹. The complexes were subjected to DNA and BSA binding studies. The complexes bound to CT-DNA either via intercalation or groove binding mode with significant binding constants for complexes whose ligands bore OH⁻ substituent. The complexes displayed moderate to high binding affinity to BSA and again the influence of the fluoro and hydroxyl substituent or thiazole moiety were noted to influence the interactions. Complexes 4 and 8 were more cytotoxic against HELA (cervical cancer cell line) compared to MDA-MB231 (breast cancer cell line) and SHSY5Y (neuronal cancer cell line), with two-fold more potent cytotoxic activity than the reference cisplatin. The complexes, as such, might be potential anticervical cancer agents.