Organotin meclofenamic complexes: Synthesis, crystal structures and antiproliferative activity of the first complexes of meclofenamic acid - Novel anti-tuberculosis agents

The complexes [Me-2(Meclo)SnOSn(Meclo)Me-2](2) (2) and [Ph3Sn(Meclo)] (3) where HMeclo is meclofenamic acid, N-(2,6-dichloro-m-tolylanthranilic acid)], have been prepared and structurally characterized by means of vibrational, H-1 and C-13 NMR spectroscopies. The crystal structure of complexes (2) and (3) have been determined by X-ray crystallography. Three distannoxane rings are present to the dimeric tetraorganodistannoxane of planar ladder arrangement of (2). The structure is centro symmetric and features a central rhombus Sn2O2 unit two additional tin atoms linked at the oxygen atoms. Five- and six-coordinated tin centers are present in the dimer distannoxane. X-ray analysis of (3) revealed a penta-coordinated structure containing Ph3Sn coordinated to the chelated carboxylato group. The polar imino hydrogen atom participates in intra-molecular hydrogen bonds. Complexes (2) and (3) are self-assembled via pi -> pi, C-H-pi, stacking interactions and intra-molecular hydrogen bonds. Meclofenamic acid and [Ph3Sn(Meclo)] have been evaluated for antiproliferative activity in vitro against three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (Madder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse L-929 (a fibroblast-like cell line cloned from strain L). The [Ph3Sn(Meclo)] complex exhibited high cytotoxic activity against all the cancer cell lines. Meclofenamic and [Ph3Sn(Meclo)] were tested for anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv. The [Ph3Sn(Meclo)] complex was found to be a promising anti-mycobacterial lead compound, displaying high activity against M. tuberculosis H37Rv. (C) 2009 Elsevier Inc. All rights reserved.