Synthesis, spectral characterisation, biocidal investigation, in-silico and molecular docking studies of 4-[(2-chloro-4-methylphenyl)carbamoyl]butanoic acid derived triorganotin(IV) compounds

Abstract

Three triorganotin(IV) compounds, R₃Sn(L), with R = CH₃ (1), n-C₄H₉ (2) and C₆H₅ (3), and LH = 4-[(2-chloro-4-methylphenyl)carbamoyl]butanoic acid, were prepared and confirmed by various techniques. A five-coordinate, distorted trigonal-bipyramidal geometry was elucidated for tin(IV) centres both in solution and solid states. An intercalation mode was confirmed for the compound SS-DNA interaction by UV-visible, viscometric techniques and molecular docking. MD simulation revealed stable binding of LH with SS-DNA. Anti-bacterial investigation revealed 2 to be generally the most potent, especially against Sa and Ab, i.e. having the lowest MIC values (≤0.25 μg/mL) compared to the standard anti-biotics vancomycin-HCl (MIC = 1 μg/mL) and colistin-sulphate (MIC = 0.25 μg/mL). Similarly, the anti-fungal profile shows 2 exhibits 100% inhibition against Ca and Cn fungal strains and has MIC values (≤0.25 μg/mL) comparatively lower than standard drug fluconazole (0.125 and 8 μg/mL for Ca and Cn, respectively). Compound 2 has the greatest activity with CC₅₀ ≤ 25 μg/mL and HC₅₀ > 32 μg/mL performed against HEC239 and RBC cell lines. The anti-cancer potential was assessed against the MG-U87 cell line, using cisplatin as the standard (133 µM), indicates 2 displays the greatest activity (IC₅₀: 5.521 µM) at a 5 µM dose. The greatest anti-leishmanial potential was observed for 2 (87.75 at 1000 μg/mL) in comparison to amphotericin B (90.67). The biological assay correlates with the observed maximum of 89% scavenging activity exhibited by 2. The Swiss-ADME data publicised the screened compounds generally follow the rule of 5 of drug-likeness and have good bioavailability potential.

Communicated by Ramaswamy H. Sarma

Keywords:

• Triorganotin(IV) compounds
• X-ray crystallography
• DNA interaction
• biocidal investigation
• in silico study

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Higher Education Commission (HEC) Pakistan is highly esteemed for financial support under NRPU Grant # 20-17572/NRPU/R&D/HEC/2021 awarded to M. Sirajuddin. CO-ADD (The Community for Antimicrobial Drug Discovery) funded by the Welcome Trust (UK) and The University of Queensland (Australia) is greatly acknowledged for performing the anti-microbial. Sunway University Sdn Bhd under Grant no. GRTIN-RRO-56-2022 is highly appreciated for structural studies.