Synthesis and mycobactericidal properties of metal complexes of isonicotinoyldithiocarbazic acid

Abstract

An isonicotinoyldithiocarbazic acid (IN-DtczH) ligand, synthesized from isoniazid, was complexed with transition metals and evaluated for anti-mycobacterial activity as well as toxicity towards human-transformed rhabdomyosarcoma (RD) cells in vitro. Complexes with Ni, Co and Zn showed MIC of 2, 2 and 50 mug/ml against Mycobacterium tuberculosis H(37)Rv, and 10, 100 and 50 mug/ml against a multidrug-resistant strain of M. tuberculosis. They had little cytotoxic effect on the RD cells. In contrast, the Cu complex was highly cytotoxic with a low anti-mycobacterial activity.

In Vitro Activity of Copper(II) Complexes, Loaded or Unloaded into a Nanostructured Lipid System, against Mycobacterium tuberculosis

“…A literature survey showed numerous Cu(II) complexes with significant antimycobacterial activity against Mtb H 37 Rv [ 6 ]. For instance, Kanwar et al [ 7 ] have described that the copper(II) derivative of isonicotinoyldithiocarbazic acid displays a minimum inhibitory concentration (MIC) value of 2 μg·mL −1 against the H 37 Rv strain. Additionally, copper(II) compounds bearing fluorinated isonicotinoylhydrazones and carboxamidrazones have demonstrated an enhanced ability to kill intracellular mycobacterium [ 6 , 8 ].…”

Methyl-2-arylidene hydrazinecarbodithioates: synthesis and biological activity

“…Many N-substituted thiosemicarbazones were prepared by the condensation of Schiff's bases of methyl-2-arylidene hydrazinecarbodithioate (MAHCD) with amines (Casero et al, 1980;Collins et al, 1982;Klayman et al, 1979Klayman et al, , 1991Scovill et al, 1982;Shipman et al, 1981). While thiosemicarbazones and their metal complexes were studied for their biological activity (Beraldo & Gambinob, 2004;Ettari et al, 2010;Jiang et al, 2006;Katz, 1987;Liberta & West, 1992;Matesanz & Souza, 2009;Pandeya & Dimmock, 1993;Wnuk & Robins, 2006;Yu et al, 2009), the intermediate MAHCD was rarely studied for its metal complexation behaviour and the complexes for their biological activity (Ali et al, 2002;Kanwar et al, *Corresponding author, e-mail: venkatesanj@bitmesra.ac.in 2008; Neelam et al, 2000;Saxena & Tandon, 1983;Singh et al, 1997). Very few investigators have reported biological activity of compounds with a dithiocarbamate side chain (Cao et al, 2005;Huang et al, 2009;Kumar et al, 2010).…”

Untitled

“…The biological activity of these compounds may be connected to their ability to form complexes with certain metal ions which may lead to a ''locked geometry'' via the coordination mechanism so that only certain substances are able to become attached to the framework of this interaction. The metal complexes of such type of ligand systems exhibit interesting metal-nitrogen and metal-sulfur bonding features with increased electron delocalization which may lead to improved biological activity 14 .…”