Carbohydrate linked organotin(iv) complexes as human topoisomerase Iα inhibitor and their antiproliferative effects against the human carcinoma cell line

Abstract

Dimethyltin(IV) complexes with ethanolamine (1) and biologically significant N-glycosides (2 and 3) were designed and synthesized. The structural elucidation of complexes 1-3 was done using elemental and spectroscopic methods; in addition, complex 1 was studied by single crystal X-ray diffraction studies. The in vitro DNA binding profile of complexes 2 and 3 was carried out by employing different biophysical methods to ascertain the feasibility of glycosylated complexes. Further, the cleaving ability of 2 and 3 was investigated by the agarose gel electrophoretic mobility assay with supercoiled pBR322 DNA, and demonstrated significantly good nuclease activity. Furthermore, both the complexes exhibited significant inhibitory effects on the catalytic activity of human Topo I at lower concentration than standard drugs. Computer-aided molecular docking techniques were used to ascertain the mode and mechanism of action towards the molecular target DNA and Topo I. The cytotoxicity of 2 and 3 against human hepatoma cancer cells (Huh7) was evaluated, which revealed significant regression in cancerous cells as compared with the standard drug. The antiproliferative activities of 2 and 3 were tested against human hepatoma cancer cells (Huh7), and results showed significantly good activity. Additionally, to validate the remarkable antiproliferative activity of complexes 2 and 3, specific regulatory gene expression (MMP-2 and TGF-β) was obtained by real time PCR.

Organo-tin antitumor compounds: Their present status in drug development and future perspectives

“…The tin-based compounds exhibit substantial binding to the phosphodiester backbone of DNA, and change the intracellular metabolism of the phospholipids of the endoplasmic reticulum [20]. The watersoluble carbohydrate appended dimethyltin(IV) complexes with ethanolamine and biologically significant N-glycosides were designed and synthesized by our group [21]. All the complexes exhibited significant inhibitory effects on the catalytic activity of human Topo I at lower concentration than standard drugs.…”

Mechanistic insights into a novel chromone-appended Cu(ii) anticancer drug entity: in vitro binding profile with DNA/RNA substrates and cytotoxic activity against MCF-7 and HepG2 cancer cells

“…In continuation of our pursuit for the design and synthesis of targeted metal based chemotherapeutic antitumor agents, 15,16 herein we have opted a new elegant modality in metal-based drug design by incorporating an endogenously biocompatible metal ion into the metal binding domain of a bioactive pharmacophore (3-formylchromone). The reaction involved first in situ methoxylation at 2-position of 3-formylchromone and then its subsequent complexation with the Cu(II) ion to yield complex 1.…”

Heteroleptic Copper(I) Complexes of “Scorpionate” Bis-pyrazolyl Carboxylate Ligand with Auxiliary Phosphine as Potential Anticancer Agents: An Insight into Cytotoxic Mode

“…The field of metallodrugs came to be recognized after the foundation laid by the serendipitous discovery of cisplatin (cis-diamminedichloroplatinum(II)). Cisplatin exhibited wide applications as a chemotherapeutic agent, but it has also been found to produce severe side effects3456789. Since then there has been a hectic search for better metal-based cancer chemotherapeutic drugs.…”