BackgroundTributyltin (IV) compounds are promising candidates for drug development. In the current study, we evaluated in-vitro and in-silico profile of carboxylate derivatives of tributyltin (IV) complexes.MethodsADMET and drug-likeliness properties were predicted using MetaPrint2D React, preADMET, SwissADME and Molsoft tools. SwissTargetPrediction predicted molecular targets for compounds. In-vitro bioactivity was evaluated by quantifying cytotoxicity against HepG2, THP-1 cell lines, isolated lymphocytes and leishmania promastigotes as well as measuring protein kinase (PK) inhibition activity.ResultsResults indicate partial compliance of compounds with drug-likeliness rules. Ch-409 complies with WDI and Lipinski rules. ADMET profile prediction shows strong plasma protein binding except for Ch-409, low to high GI absorption and BBB penetration (Cbrain/Cblood = 0.942–11; caco-2 cells permeability 20.13–26.75 nm/sec), potential efflux by P-glycoprotein, metabolism by CYP3A4, medium inhibition of hERG, mutagenicity and capacity to be detoxified by glutathionation and glucuronidation. Molecular targets include proteases, enzymes, membrane receptors, transporters and ion channels where Ch-409 targets membrane receptors only. Compounds are significantly (p < 0.05) cytotoxic against HepG2 cell line and leishmania as compared with normal isolated lymphocytes. Ch-459 indicates highest toxicity against leishmania (mortality 97.9 ± 3.99%; LC50 0.323 ± 0.002 μg/mL) whereas Ch-409 possesses maximum cytotoxicity against HepG2 cell line (IC50 0.08 ± 0.001 μg/mL) as well as 97.5 ± 1.98% (LC50 0.954 ± 0.158 μg/mL) mortality of leishmania promastigotes. It was observed that antileishmanial effect was reduced by 16.38%–34.38% and 15–38.2% in the presence of NaN3 and mannitol respectively. PK inhibition and reactive oxygen species production are possible mechanisms for cytotoxicity.ConclusionsSelected carboxylate derivatives of tributyltin (IV) complexes possess significant antileishmanial and cytotoxic potential. These are promising compounds for the development of antileishmanial and anticancer drugs.
Graphical AbstractCarboxylate derivatives of tributyltin (IV) complexes as anticancer and antileishmanial agents
Herein, we report synthesis of novel organotin(IV) carboxylates i.e; [(C6H5)3Sn(C10H14NO3)] B1 and [(C4H9)3Sn(C10H14NO3)] B2 by reacting triphenyltin hydroxide and bis(tributyltin) oxide with as‐prepared ligand 3‐cyclohexylcarbamoyl‐acrylic acid A under inert atmosphere. The as‐synthesized complexes were characterized by elemental analysis (CHNS), fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy(1H‐NMR, 13C‐NMR) and mass spectrometry (EI‐MS). The structures of both as‐prepared tin complexes B1 and B2 were determined by single crystal X‐ray crystallography. Thermogravimetric analysis has shown single step decomposition of both these complexes. The as‐prepared complexes were used as single source precursor for the deposition of tin oxide thin films at 350 °C and 400 °C by aerosol assisted chemical deposition (AACVD) on bare and at 400 °C on carbon nanodots pre‐coated glass substrate. The as‐deposited thin films were characterized by powdered X‐rays diffraction (pXRD), field emission scanning electron microscope (FE‐SEM) and energy dispersive X‐rays spectroscopy (EDX). Furthermore, antimicrobial, anti‐oxidant and cytotoxicity studies of both complexes showed moderate to good biological activities. Thus, as‐prepared novel complexes have potential applications in materials as‐well as in medicinal chemistry.
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