Cytotoxic potential of novel selenolato-bridged manganese(I)-based CORM and its molecular interaction with human serum albumin and DNA through spectroscopic and in silico docking studies.

The prevalence of cancer is increasing steadily over the past few decades due to social and environmental factors. Several drugs and medications have also been reported, but with inevitable side effects. Herein comes the urgent need for the development of precision medicine, which increases the efficiency of the drug on the target tissue and minimizes systemic toxicity and non-specificity. One of the several approaches developed includes the formulation of smart or trigger-specific drugs for spatiotemporal delivery. In this view, an arena of carbon monoxide-releasing molecules (CORMs) that could be rendered trigger-specific using labile ligands has been developed. In the present investigation, one such novel, manganese based CORM (Mn-CORM) was synthesized and analysed for its selective cytotoxic potential. The Mn-CORM exerted a broad-spectrum cytotoxicity against cancer cells such as PAN C1 (pancreatic cancer), PC 3 (prostate cancer) and HT 29 (colon cancer). Present study further investigated the binding potential of Mn-CORM for human serum albumin (HSA), the major transporter of anticancer drugs and DNA using a multi-spectroscopic (UV-VIS absorption, quenching analysis, time resolved fluorescence spectroscopy, circular dichroism spectroscopy) and molecular docking techniques. The analysis of thermodynamic parameters ΔSand ΔH showed that the binding of Mn-CORM to HSA was spontaneous and dominated by Van der Waals forces and hydrogen bonding. The binding potential of Mn-CORM for CT DNA was also investigated using spectroscopic studies, dye displacement assay, circular dichroism spectroscopy, thermal denaturation and DNA cleavage studies. Results demonstrated a good binding potential of Mn-CORM for CT DNA. The probable mode of binding of Mn-CORM and CT DNA was concluded to be a partial intercalation. All these experimental and computational results confirmed that the novel Mn-CORM used in the present study can be a promising anticancer agent.