Synthesis, spectral, in silico/molecular docking and pharmacological studies of biologically potent triorganotin(IV) carboxylates

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A series of compounds containing a glutaric anhydride-based carboxylate ligand (LH) and three triorganotin derivatives R3SnL for R = Me (1), nBu (2), and pH (3) are described in this article. The synthesis of the compounds was confirmed by microelemental CHN analysis, FT-IR, NMR and in the case of LH, 1 and 2 by single crystal X-ray crystallography, revealing the formation of one-dimensional coordination polymers for 1 and 2 with trans-C3O2 trigonal-bipyramidal geometries for the tin(IV) atoms. The anti-microbial activity was explored with the MIC values of 2 (≤ 0.25 µg/mL against the bacterium S. aureus and fungal strains C. albicans and C. neoformans) being less than observed for the anti-bacterial drug vancomycin-HCl (1 μg/mL) and anti-fungal drug fluconazole (≤ 0.25 and 8 μg/mL, respectively). The maximum cytotoxicity was observed for 2, against the human embryonic kidney (HEC239) cell line, with CC50 ≤ 25 μg/mL. An evaluation of the compound-DNA interactions was performed through UV–Visible spectroscopic and viscometric experiments, with the observation of hypochromic along with slight bathochromic shifts and an increase in viscosity, respectively, revealing an intercalative mode of interaction. In comparison with the standard anti-oxidant ascorbic acid, the greatest scavenging of DPPH was recorded for 3 followed by 2, 1 and LH. The human malignant glioma cell line (MG-U87) was used to explore the anti-cancer potential of the synthesised compounds. Compounds 3 and 2 (IC50 = 5 and 21 µM, respectively) showed encouraging results when compared to cisplatin (IC50 = 133 µM). The anti-leishmanial data shows that at a 1000 µg/mL dose, the greatest percentage inhibition was observed for 2 (87.15 ± 0.01 %) which is almost equivalent to that for amphotericin B (90.67 ± 0.15 %). The docking results with SS-DNA revealed the compounds undergo an intercalative mode of interaction with the nitrogenous bases adenine, guanine and cytosine, with docking score order: 3 (-8.11) > 2 (-8.02) > 1 (-6.99) > LH (-6.38). Similarly, the docking results against the Brest cancer receptor BRCA2, indicate the highest binding score was observed for 3. The anti-leishmanial docking data indicates 2 as having maximum docking score (-7.79). The in silico study, performed to reveal the drug-likeness behaviour of the news compounds, suggest that they possess the properties of orally active drugs.