Hydrazone-containing organotin(IV) complexes: synthesis, characterization, antimicrobial, antioxidant activity and molecular-docking studies.

The diorganotin(IV) complexes (5-20) were synthesized in the present research from 4-fluorophenoxyacetic hydrazide and salicylaldehyde derivatives-based hydrazone ligands (1-4) to get an effective biological agent to combat microbial and oxidant deformities. Numerous spectral techniques such as (1H, 13C, 119Sn) NMR, UV-Vis, IR, and mass spectrometry were executed to illuminate the composition of complexes. These techniques ascertained tridentate chelation of hydrazone ligands with tin metal through enolic, phenolic oxygens and imine nitrogen, revealing pentacoordinated geometry of the complexes. The single crystal XRD of complex (5) confirmed distorted trigonal bipyramidal geometry. The TGA studies showed thermal stability up to 180 °C of the complexes, whereas the low conductance observed pointed to the non-electrolytic nature of the compounds. Furthermore, serial dilution assay was implemented to uncover the microbial inhibition efficacy (against six strains) of the compounds using ciprofloxacin and fluconazole. Among the synthesized compounds, (1, 8) exhibited comparable MIC value to standard. The compound (8) was reported as four times more potent than the fluconazole against C. albicans. Using DPPH assay, the antioxidant efficiency was examined which advocates enhanced efficacy of complexes than the ligands. The potency of complex (8) against C. albicans makes it a point of interest for molecular docking investigation, so, complex (8) and its ligand (1) were studied against protein of C. albicans (5TZ1), revealing the more efficacy of complex (binding energy-11.6 kcal/mol) than ligand. Further, the compounds were analysed for ADME prediction which concluded the efficacy of compounds as orally efficient pharmaceuticals.

Recent Advancements in Organotin(IV) Complexes as Potent Cytotoxic Agents.

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.

A prospective multicenter cohort study of the association between global tissue hypoxia and coagulation abnormalities during early sepsis resuscitation.

OBJECTIVE: Coagulation activation is an integral part of sepsis pathogenesis. Experimental data suggest that endothelial exposure to hypoxia activates coagulation. We aimed to test the hypothesis that the quantity of exposure to global tissue hypoxia is associated with the degree of coagulation activation during early sepsis resuscitation. DESIGN: Prospective, multicenter cohort study. SETTING: Emergency department and intensive care unit of three academic hospitals. PATIENTS: Inclusion criteria were age older than 17, acute infection with two or more signs of systemic inflammation, hypotension despite fluid challenge (or lactate >4 mM), and continuous central venous oxygen saturation (Scvo2) monitoring for quantitative resuscitation. Exclusion criteria were anticoagulant or blood product administration. MEASUREMENTS AND MAIN RESULTS: We recorded central venous oxygen saturation continuously for 0 to 6 hrs of resuscitation and calculated the area under the curve for central venous oxygen saturation <70%. We defined hypoxia exposure as exceeding the median area under the curve for the entire cohort. At 0, 6, and 24 hrs, we measured conventional coagulation biomarkers plus thrombin-antithrombin complex, plasmin-antiplasmin complex, tissue plasminogen activator, plasminogen activator inhibitor-1, protein C, antithrombin, and endothelial markers (E-selectin, intracellular adhesion molecule-1, thrombomodulin). We compared changes during 0 to 6 hrs and 0 to 24 hrs in biomarkers between hypoxia exposure and nonexposure groups. We enrolled 40 patients (60% requiring vasopressors; 30% mortality). We found that exposure to hypoxia alone was not associated with a significant degree of coagulation activation. However, in secondary analyses we found that exposure to arterial hypotension induced E-selectin and thrombin-antithrombin complex, whereas concomitant exposure to both hypotension and hypoxia was associated with amplification of E-selectin and thrombomodulin, and a reduction in protein C. CONCLUSION: In this sample of patients undergoing quantitative resuscitation for sepsis, we found that exposure to global tissue hypoxia (as quantified by low central venous oxygen saturation) was not associated with major coagulation activation. Further investigation to elucidate the clinical factors that trigger or intensify the procoagulant response to sepsis is warranted.