Carboxylate derivatives of tributyltin (IV) complexes as anticancer and antileishmanial agents

• DOI: 10.1186/s40199-017-0174-0
• Publication Date: 2017-04-05T02:29:37Z
• Authors: Durdana Waseem; Arshad Farooq Butt; Ihsan-ul Haq; Moazzam Hussain B...; Gul Majid Khan
• Keywords: Carboxylate

Tributyltin (IV) compounds are promising candidates for drug development. In the current study, we evaluated in-vitro and in-silico profile of carboxylate derivatives tributyltin complexes.ADMET drug-likeliness properties were predicted using MetaPrint2D React, preADMET, SwissADME Molsoft tools. SwissTargetPrediction molecular targets compounds. In-vitro bioactivity was by quantifying cytotoxicity against HepG2, THP-1 cell lines, isolated lymphocytes leishmania promastigotes as well measuring protein kinase (PK) inhibition activity.Results indicate partial compliance with rules. Ch-409 complies WDI Lipinski ADMET prediction shows strong plasma binding except Ch-409, low to high GI absorption BBB penetration (Cbrain/Cblood = 0.942-11; caco-2 cells permeability 20.13-26.75 nm/sec), potential efflux P-glycoprotein, metabolism CYP3A4, medium hERG, mutagenicity capacity be detoxified glutathionation glucuronidation. Molecular include proteases, enzymes, membrane receptors, transporters ion channels where receptors only. Compounds significantly (p < 0.05) cytotoxic HepG2 line compared normal lymphocytes. Ch-459 indicates highest toxicity (mortality 97.9 ± 3.99%; LC50 0.323 0.002 μg/mL) whereas possesses maximum (IC50 0.08 0.001 97.5 1.98% (LC50 0.954 0.158 mortality promastigotes. It observed that antileishmanial effect reduced 16.38%-34.38% 15-38.2% in presence NaN3 mannitol respectively. PK reactive oxygen species production possible mechanisms cytotoxicity.Selected complexes possess significant potential. These development anticancer drugs. Graphical Abstract Carboxylate agents.