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 [Ph(3)Sn(Meclo)] (3) where HMeclo is meclofenamic acid, N-(2,6-dichloro-m-tolylanthranilic acid)], have been prepared and structurally characterized by means of vibrational, (1)H and (13)C 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 Sn(2)O(2) 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 Ph(3)Sn 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 [Ph(3)Sn(Meclo)] have been evaluated for antiproliferative activity in vitro against three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder 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 [Ph(3)Sn(Meclo)] complex exhibited high cytotoxic activity against all the cancer cell lines. Meclofenamic and [Ph(3)Sn(Meclo)] were tested for anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv. The [Ph(3)Sn(Meclo)] complex was found to be a promising anti-mycobacterial lead compound, displaying high activity against M. tuberculosis H37Rv.
Kovala-Demertzi
Dimitra
D
Department of Chemistry, University of Ioannina, Greece. dkovala@cc.uoi.gr
Dokorou
Vaso
V
Primikiri
Alexandra
A
Vargas
Richy
R
Silvestru
Cristian
C
Russo
Umberto
U
Demertzis
Mavroudis A
MA
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018360:Crystallography, X-Ray; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008469:Meclofenamic Acid / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009947:Organotin Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000995:Antitubercular Agents; D009947:Organotin Compounds; D008469:Meclofenamic Acid; C030665:triphenyltin