ABSTRACT
Malaria, a relentless and ancient adversary, continues to cast its shadow over vast swathes of the globe, afflicting millions of people and have a heavy toll on human health and well-being. Despite substantial progress in the fight against this parasitic disease in recent decades, malaria still persists as a substantial global health concern, especially in some specific region which have limited resources and vulnerable populations. Thus, to ascertain an combating agent for malaria and its associated dysfunction, 4-(4-ethylphenyl)-3-thiosemicarbazide and benzaldehydes based two new thiosemicarbazone ligands (1-2) and their cobalt(II), nickel(II), copper(II), zinc(II) metal complexes (3-10) were synthesized in the present research work. The synthesized compounds were comprehensive characterized through spectral and physical investigations, demonstrating octahedral stereochemistry of the complexes. Further, the antimalarial and antioxidant potential of the compounds (1-10) were analyzed by micro assay and DPPH assay protocols, respectively, to examine the therapeutic aspect of the compounds. The performed biological evaluations revealed that the complexes are more efficient in controlling infectious ailment in comparison of ligands. The complexes (5), (6), (10) shows significant efficiency for malarial and oxidant dysfunctions whereas Zn(II) complex (6) exhibit highest potency with 1.02 ± 0.07 and 2.28 ± 0.05 µM IC50 value. Furthermore, to support the highest antimalarial potency of the (3-6) complexes and their associated ligand (1), the computational studies like molecular docking, DFT, MESP and ADMET analysis were executed which were supported the biological efficacy of the complex (6) by providing numerous parameters like binding interaction electronegativity, electrophilicity, HOMO value and electron density.
Subject(s)
Antimalarials , Coordination Complexes , Malaria , Thiosemicarbazones , Humans , Antimalarials/pharmacology , Antimalarials/chemistry , Molecular Docking Simulation , Antioxidants/pharmacology , Antioxidants/chemistry , Thiosemicarbazones/pharmacology , Thiosemicarbazones/chemistry , Ligands , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Zinc/chemistry , Copper/chemistry , Chelating AgentsABSTRACT
BACKGROUND: Cancer cases have escalated by approximately 12% since 1900 and the incidence rate has increased faster for females than males. The discovery of cisplatin in 1965 paved the way for metal-based compounds as cancer therapeutics. Unfortunately, cisplatin and other platinum-based medicines cause severe side effects. Therefore, non-platinum metal complexes have been developed as alternate cancer drugs. Among non-platinum metal complexes, organotins are the most effective candidates in oncology due to their wide range of anticancer activities with relatively minimal toxicities towards healthy cells, better excretion from the body, and fewer side effects than platinum drugs. METHODS: Using DOI searching, advances made by organotin(IV) complexes coordinated with Sn-O, Sn-N and Sn-S as chemotherapeutic agents since 2018 are summarized in this article. Their chemical structure and in vitro antiproliferative activity in terms of IC50/EC50/LD50 are cumulated. RESULTS: As reflected in this perspective, organotin(IV) complexes are found to induce high cell death via apoptosis, and also several complexes demonstrated anticancer activity even higher than standard drugs. CONCLUSION: Undoubtedly, the organotin(IV) complexes could bring hope to morbidity and mortality of human beings caused by fast-spreading cancer worldwide and can play an important role in drug discovery.
