Antimitotic activity of structurally simplified biaryl analogs of the anticancer agents colchicine and combretastatin A4.

Two substituted biaryl analogues of colchicine and combretastatin A4, readily available through a one-step, protecting group free Suzuki-Miyaura reaction were discovered to exhibit anticancer activity while simultaneously being of low cytotoxicity to noncancerous cell lines. The compounds were shown to initiate apoptosis selectively via a mechanism involving inhibition of tubulin polymerization.

Nonprocessive [2 + 2]e- off-loading reductase domains from mycobacterial nonribosomal peptide synthetases.

In mycobacteria, polyketide synthases and nonribosomal peptide synthetases (NRPSs) produce complex lipidic metabolites by using a thio-template mechanism of catalysis. In this study, we demonstrate that off-loading reductase (R) domain of mycobacterial NRPSs performs two consecutive [2 + 2]e(-) reductions to release thioester-bound lipopeptides as corresponding alcohols, using a nonprocessive mechanism of catalysis. The first crystal structure of an R domain from Mycobacterium tuberculosis NRPS provides strong support to this mechanistic model and suggests that the displacement of intermediate would be required for cofactor recycling. We show that 4e(-) reductases produce alcohols through a committed aldehyde intermediate, and the reduction of this intermediate is at least 10 times more efficient than the thioester-substrate. Structural and biochemical studies also provide evidence for the conformational changes associated with the reductive cycle. Further, we show that the large substrate-binding pocket with a hydrophobic platform accounts for the remarkable substrate promiscuity of these domains. Our studies present an elegant example of the recruitment of a canonical short-chain dehydrogenase/reductase family member as an off-loading domain in the context of assembly-line enzymology.

N-terminally modified linear and branched spermine backbone dipeptidomimetics against planktonic and sessile methicillin-resistant Staphylococcus aureus.

Toward the discovery of useful therapeutic molecules, we report the design and synthesis of a focused library of new ultrashort N-terminally modified dipeptidomimetics, with or without modifications in the spermine backbone leading to linear (series 1) or branched (series 2) tryptophans, as antimicrobial agents. Eight peptidomimetics in the library showed good antibacterial activity (MICs of 1.77 to 14.2 µg/ml) against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis bacterial strains. Tryptophan fluorescence measurements on artificial bacterial or mammalian mimic membranes and assessment of the MRSA potential depolarization ability of the designed compounds revealed membrane interactions dependent on tryptophan positioning and N-terminal tagging. Among active peptidomimetics, compounds 1c and 1d were found to be nonhemolytic, displaying rapid bactericidal activity (at 4× MIC) against exponentially growing MRSA. Further, scanning electron microscopy of peptidomimetic 1c- and 1d-treated MRSA showed morphological changes with damage to cell walls, defining a membrane-active mode of action. Moreover, peptidomimetics 1c and 1d did not induce significant drug resistance in MRSA even after 17 passages. We also investigated the activity of these molecules against MRSA biofilms. At sub-MIC levels (∼2 to 4 µg/ml), both peptidomimetics inhibited biofilm formation. At concentrations higher than the MIC (35 to 140 µg/ml), peptidomimetics 1c and 1d significantly reduced the metabolic activity and biomass of mature (24-h) MRSA biofilms. These results were corroborated by confocal laser scanning microscopy (live/dead assay). The in vitro protease stability and lower cytotoxicity of peptidomimetics against peripheral blood mononuclear cells (PBMCs) support them being novel staphylocidal peptidomimetics. In conclusion, this study provides two peptidomimetics as potential leads for treatment of staphylococcal infections under planktonic and sessile conditions.

Household Influenza Transmission and Healthcare Resource Utilization Among Patients Treated with Baloxavir vs Oseltamivir: A United States Outpatient Prospective Survey.

INTRODUCTION: Influenza is a common, seasonal infectious disease with broad medical, economic, and social consequences. Real-world evidence on the effect of influenza treatment on household transmission and healthcare resource utilization is limited in outpatient settings in the USA. This study examined the real-world effectiveness of baloxavir vs oseltamivir in reducing influenza household transmission and healthcare resource utilization. METHODS: This prospective electronic survey on patient-reported outcomes was conducted between October 2022 and May 2023 via CVS Pharmacy in the USA. Adult participants (≥ 18 years old) were eligible if they filled a prescription for baloxavir or oseltamivir at a CVS Pharmacy within 2 days of influenza symptom onset. Participant demographics, household transmission, and all-cause healthcare resource utilization were collected. Transmission and utilization outcomes were assessed using χ2 and Fisher exact tests. RESULTS: Of 87,871 unique patients contacted, 1346 (1.5%) consented. Of 374 eligible patients, 286 (90 baloxavir- and 196 oseltamivir-treated patients) completed the survey and were included in the analysis. Mean age of participants was 45.4 years, 65.6% were female, and 86.7% were White. Lower household transmission was observed with baloxavir compared with oseltamivir therapy (17.8% vs 26.5%; relative risk = 0.67; 95% CI 0.41-1.11). Healthcare resource utilization, particularly emergency department visits (0.0% vs 4.6%), was also numerically lower in the baloxavir-treated group; no hospitalizations were reported in either cohort. CONCLUSIONS: The findings from this real-world study suggest that antiviral treatment of influenza with baloxavir may decrease household transmission and reduce healthcare resource utilization compared with oseltamivir.

Control of SARS-CoV-2 infection in skilled nursing facilities in Detroit, Michigan: a model for emerging infectious diseases.

An infection prevention bundle that consisted of the development of a response team, public-academic partnership, daily assessment, regular testing, isolation, and environmental controls was implemented in 26 skilled nursing facilities in Detroit, Michigan (March 2020-April 2021). This intervention was associated with sustained control of severe acute respiratory coronavirus virus 2 infection among residents and staff.

CNS tuberculoma in an immunocompetent patient: A case report of multi-drug hypersensitivity to RIPE therapy.

Background: Tuberculosis (TB) is the second leading cause of death due to an infectious disease worldwide (World Health Organization, 2022 [1]). The first line treatment of TB involves the concurrent use of four drugs: rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE). Given the rising threat of multidrug resistant TB, it is crucial to understand how TB can be treated when first line treatment is not an option. Case presentation: We report a rare case of multi-drug hypersensitivity to RIPE therapy in an immunocompetent patient with an unusual presentation of CNS tuberculoma. The patient presented to an outside hospital four months prior with weakness, numbness, imbalance, and speech difficulties. A CT of the head revealed a mass in the left parietal lobe that demonstrated chronic necrotizing granulomatous inflammation with positive cultures for M. tuberculosis. The patient was started on a regimen of rifampin 600 mg daily, isoniazid 300 mg daily, pyrazinamide 2000 mg daily, ethambutol 1200 mg daily, and pyridoxine 50 mg daily. However, the patient developed drug hypersensitivity reactions to both rifampin and ethambutol with subsequent failed desensitization to rifabutin. She was ultimately discharged from the hospital on a regimen of isoniazid, pyridoxine, pyrazinamide, and moxifloxacin with plans for outpatient follow-up. Conclusions: This case highlights a rare clinical presentation of multiple drug hypersensitivity in the setting of a CNS tuberculoma and the importance of identifying the offending agents early in the course of treatment and adjusting the drug regimen accordingly. Desensitization should be attempted, but if ineffective, then alternative drug regimens should be formulated on a case-by-case basis.

Medicinal applications of vanadium complexes with Schiff bases.

Many transition metal complexes have been explored for their therapeutic properties after the discovery of cisplatin. Schiff bases have an efficient complexation tendency with the transition metals and several medicinal properties have been reported. However, fewer studies have reported the medicinal utility of vanadium and its Schiff base complexes. This paper provides a comprehensive overview of vanadium complexes with Schiff bases along with their mechanistic insight. Vanadium complexes in + 4 and + 5 oxidation states have exhibited well-defined geometry and found to be thermodynamically stable. The studies have reported the G0/G1 phase cell cycle arrest and decreased delta psi m, inducing mitochondrial membrane depolarization in cancer cell lines along with the alterations in the metabolism of the cancer cells upon dosing with the vanadium complexes. Cancer cell invasion and growth are also found to be markedly reduced by peroxo complexes of vanadium. The studies included in the review paper have been taken from leading indexing databases and focus was laid on recent reports in literature. The biological potential of vanadium complexes of Schiff bases opens new horizons for future interdisciplinary studies and investigation focussed on understanding the biochemistry of these complexes, along with designing new complexes which have better bioavailability, solubility and low or non-toxicity.

COVID-19 vaccination up-take in three districts of Nepal.

Vaccine hesitancy during the COVID-19 pandemic continues to be an issue in terms of global efforts to decrease transmission rates. Despite high demand for the vaccines in Nepal, the country still contends with challenges related to vaccine accessibility, equitable vaccine distribution, and vaccine hesitancy. Study objectives were to identify: 1) up-take and intention for use of COVID-19 vaccines, 2) factors associated with vaccine up-take, and 3) trusted communication strategies about COVID-19 and the vaccines. A quantitative survey was implemented in August and September 2021 through an initiative at the Nepali Ministry of Health and Population Department of Health Services, Family Welfare Division. Data were collected from 865 respondents in three provinces (Bagmati, Lumbini, and Province 1). Ordinal multivariate logistic regression was utilized to determine relationships between vaccination status and associated factors. Overall, 62% (537) respondents were fully vaccinated and 18% (159) were partially vaccinated. Those respondents with higher education (p < .001) and higher household income (p < .001) were more likely vaccinated. There were also significant differences in vaccine up-take across the three provinces (p < .001). Respondents who were vaccinated were significantly more likely to perceive vaccines as efficacious in terms of preventing COVID-19 (p = .004) and preventing serious outcomes (p = .010). Among both vaccinated and unvaccinated individuals, there was a high level of trust in information about COVID-19 vaccines provided through local health-care workers [e.g. nurses and physicians]. These results are consistent with other findings within the South Asia region. Targeted advocacy and outreach efforts are needed to support ongoing COVID-19 vaccination campaigns throughout Nepal.

Synthesis, antibacterial activity and mode of action of novel linoleic acid-dipeptide-spermidine conjugates.

Towards therapeutically viable mimics of host defense cationic peptides (HDCPs) here we report the design and synthesis of a small library, based on a novel hydrophobic-dipeptide-spermidine template. Lipidated sequences 11, 14, 15, 16, 18 and 19 exhibited potent activity against susceptible as well as drug resistant Gram-positive and Gram-negative bacterial strains. Structure-activity relationships of the template revealed a hydrophobicity window of 50-70% with minimum +2 charges to be crucial for activity and cell selectivity. Active sequences 14, 15 and 16 exhibited different modes of action based on dipeptide composition as revealed by studies on model membranes, intact bacterial cells and DNA. Further, severe damage to surface morphology of methicillin resistant S. aureus caused by 14, 15 and 16 at 10 × MIC was observed. The present study provides us two active sequences (14 and 16) with a membrane perturbing mode of action, cell selectivity to hRBCs and keratinocytes along with potent activity against clinically relevant pathogen MRSA. The designed template thus may prove to be a suitable probe to optimize sequences for better selectivity and potential to combat a wide range of drug resistant strains in further research.

Synthesis and antitubercular activity evaluation of novel unsymmetrical cyclohexane-1,2-diamine derivatives.

A library of unsymmetrical cyclohexane-1,2-diamine derivatives were synthesized and evaluated for their activity against Mycobacterium tuberculosis H37Rv in vitro. Out of the 46 compounds synthesized, eight compounds (11h, 13a, 13e, 13f, 14a, 14c, 14d, and 15d) were found to be active at or below 6.25 µM concentration, with negligible toxicity to human red blood cells at a concentration much higher than the MIC(99) . Compound 13a was the best active compound showing inhibition at 3.125-6.25 µM, and was found to be non-hemolytic up to 500 µg/mL concentration.

Efficacy and Toxicity Studies of Novel α-MSH Analogues with Antibiofilm Action and ß-Lactam Resensitization Potential against MRSA.

Methicillin-resistant Staphylococcus aureus (MRSA), a biofilm-forming recalcitrant pathogen with a multidrug-resistant profile, poses a pandemic threat to human health and is the leading cause of severe infections in both healthcare and community settings. In this study, toward designing novel α-MSH-based peptides with enhanced activity and stability against MRSA, particularly its stationary phase and biofilm, we explored a design approach to augment the hydrophobicity of an 8-mer C-terminal α-MSH(6-13)-based peptide Ana-5 through the incorporation of a bulky unnatural amino acid. The designed Ana-peptides overcame the limitation of diminished activity in biological media and exhibited enhanced antistaphylococcal activity and cell selectivity. With membrane rupture as the primary mode of action, the peptides exhibited inhibitory potential against S. aureus biofilms. Importantly, the peptides did not exhibit any adverse effects in the in vivo toxicity studies and were also able to significantly alleviate bacterial infection in a systemic infection mice model study. Additionally, the peptides retained their activity in the presence of serum and displayed a low propensity toward resistance development in MRSA cells. Moreover, the observed synergistic potential of Ana-10 with conventional antibiotics could be vital in resurrecting discarded antibiotics. Thus, this study provides us with an exciting lead, Ana-10, for further development against biofilm-based chronic S. aureus infections.

The Impact of a Post-Prescription Review and Feedback Antimicrobial Stewardship Program in Lebanon.

Antimicrobial stewardship programs (ASPs) are effective means to optimize prescribing practices. They are under-utilized in the Middle East where many challenges exist for ASP implementation. We assessed the effectiveness of infectious disease physician-driven post-prescription review and feedback as an ASP in Lebanon. This prospective cohort study was conducted over an 18-month period in the medical, surgical, and intensive care units of a tertiary care hospital. It consisted of three phases: the baseline, intervention, and follow-up. There was a washout period of two months between each phase. Patients aged ≥16 years receiving 48 h of antibiotics were included. During the intervention phase, the AMS team reviewed antimicrobial use within 72 h post-prescription and gave alternate recommendations based on the guidelines for use. The acceptance of the recommendations was measured at 72 h. The primary outcome of the study was days of therapy per 1000 study patient days. A total of 328 patients were recruited in the baseline phase (August−October 2020), 467 patients in the intervention phase (January−June 2021), and 301 patients in the post-intervention phase (September−December 2021). The total days of therapy decreased from 11.46 during the baseline phase to 8.64 during the intervention phase (p < 0.001). Intervention acceptance occurred 88.5% of the time. The infectious disease physician-driven implementation of an ASP was successful in reducing antibiotic utilization in an acute care setting in Lebanon.

Low- Versus High-Dose Methylprednisolone in Adult Patients With Coronavirus Disease 2019: Less Is More.

BACKGROUND: Corticosteroids use in severe coronavirus disease 2019 (COVID-19) improves survival; however, the optimal dose is not established. We aim to evaluate clinical outcomes in patients with severe COVID-19 receiving high-dose corticosteroids (HDC) versus low-dose corticosteroids (LDC). METHODS: This was a quasi-experimental study conducted at a large, quaternary care center in Michigan. A corticosteroid dose change was implemented in the standardized institutional treatment protocol on November 17, 2020. All patients admitted with severe COVID-19 that received corticosteroids were included. Consecutive patients in the HDC group (September 1 to November 15, 2020) were compared to the LDC group (November 30, 2020 to January 20, 2021). High-dose corticosteroids was defined as 80 mg of methylprednisolone daily in 2 divided doses, and LDC was defined as 32-40 mg of methylprednisolone daily in 2 divided doses. The primary outcome was all-cause 28-day mortality. Secondary outcomes included progression to mechanical ventilation, hospital length of stay (LOS), discharge on supplemental oxygen, and corticosteroid-associated adverse events. RESULTS: Four-hundred seventy patients were included: 218 (46%) and 252 (54%) in the HDC and LDC groups, respectively. No difference was observed in 28-day mortality (14.5% vs 13.5%, P = .712). This finding remained intact when controlling for additional variables (odds ratio, 0.947; confidence interval, 0.515-1.742; P = .861). Median hospital LOS was 6 and 5 days in the HDC and LDC groups, respectively (P < .001). No differences were noted in any of the other secondary outcomes. CONCLUSIONS: Low-dose methylprednisolone had comparable outcomes including mortality to high-dose methylprednisolone for the treatment of severe COVID-19.

Interaction studies of novel cell selective antimicrobial peptides with model membranes and E. coli ATCC 11775.

Cationic antimicrobial peptides (CAMPs) are novel candidates for drug development. Here we describe design of six short and potent CAMPs (SA-1 to SA-6) based on a minimalist template of 12 residues H+HHG+HH+HH+NH2 (where H: hydrophobic amino acid and +: charged hydrophilic amino acid). Designed peptides exhibit good antibacterial activity in micro molar concentration range (1-32 mug/ml) and rapid clearance of Gram-positive and Gram-negative bacterial strains at concentrations higher than MIC. For elucidating mode of action of designed peptides various biophysical studies including CD and Trp fluorescence were performed using model membranes. Further based on activity, selectivity and membrane bound structure; modes of action of Trp rich peptide SA-3 and template based peptide SA-4 were compared. Calcein dye leakage and transmission electron microscopic studies with model membranes exhibited selective membrane active mode of action for peptide SA-3 and SA-4. Extending our work from model membranes to intact E. coli ATCC 11775 in scanning electron micrographs we could visualize different patterns of surface perturbation caused by peptide SA-3 and SA-4. Further at low concentration rapid translocation of FITC-tagged peptide SA-3 into the cytoplasm of E. coli cells without concomitant membrane perturbation indicates involvement of intracellular targeting mechanism as an alternate mode of action as was also evidenced in DNA retardation assay. For peptide SA-4 concentration dependent translocation into the bacterial cytoplasm along with membrane perturbation was observed. Establishment of a non specific membrane lytic mode of action of these peptides makes them suitable candidates for drug development.

Vancomycin-Resistant Enterococci: Epidemiology, Infection Prevention, and Control.

Vancomycin-resistant enterococcus (VRE) is a pathogen of growing concern due to increasing development of antibiotic resistance, increasing length of hospitalizations and excess mortality. The utility of some infection control practices are debatable, as newer developments in infection prevention strategies continued to be discovered. This article summarizes the significance of VRE and VRE transmission, along with highlighting key changes in infection control practices within the past 5 years.

Mixed Ligand-metal Complexes of 2-(butan-2-ylidene) Hydrazinecarbothioamide- Synthesis, Characterization, Computer-Aided Drug Character Evaluation and in vitro Biological Activity Assessment.

BACKGROUND: Mixed ligand-metal complexes are efficient chelating agents because of their flexible donor ability. Mixed ligand complexes containing hetero atoms sulphur, nitrogen and oxygen have been probed for their biological significance. METHODS: Nine mixed ligand-metal complexes of 2-(butan-2-ylidene) hydrazinecarbothioamide (2- butanone thiosemicarbazone) with pyridine, bipyridine and 2-picoline as co-ligands were synthesized with Cu, Co and Zn salts. The complexes were tested against MDA-MB231 (MDA) and A549 cell lines. Antibacterial activity was tested against Staphylococcus aureus and Escherichia coli. The drug character of the complexes was evaluated on parameters viz. physicochemical properties, bioactivity scores, toxicity assessment and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) profile using various automated softwares. Molecular docking was performed against Ribonucleotide Reductase (RR) and topoisomerase II (topo II). RESULTS: The mixed ligand-metal complexes were synthesized by condensation reaction for 4-5 h. The characterization was done by elemental analysis, 1H-NMR, FT-IR, molar conductance and UV spectroscopic techniques. Molecular docking results showed that [Cu(C5H11N3S)(py)2(CH3COO)2], [Zn(C5H11N3S)(bpy)(SO4)] and [Zn(C5H11N3S)(2-pic)2(SO4)] displayed the lowest binding energies with respect to RR. Against topo II [Cu(C5H11N3S)(py)2(CH3COO)2], [Cu(C5H11N3S)(bpy)(CH3COO)2] and [Zn(C5H11N3S)(2-pic)2(SO4)] had the lowest energies. The druglikness assessment was done using Leadlikeness and Lipinski's rules. Not more than two violations were obtained in case of each filtering rule showing drug-like character of the mixed ligand complexes. Some of the complexes exhibited positive bioactivity scores and almost all the complexes were predicted to be safe with no hazardous effects as predicted by the toxicity assessment. Ames test predicted the non-mutagenic nature of the complexes. CONCLUSION: In vitro activity evaluation showed that [Zn(C5H11N3S)(py)2(SO4)], [Co(C5H11N3S(bpy) (Cl)2] and [Cu(C5H11N3S)(2-pic)2(CH3COO)2] were active against MDA. Against A549 [Co(C5H11N3S)(py)2(Cl)2], [Cu(C5H11N3S)(py)2(CH3COO)2] and [Co(C5H11N3S(bpy)(Cl)2] were active. Antibacterial evaluation showed that [Co(C5H11N3S)(bpy)(Cl)2], [Zn(C5H11N3S)(2-pic)2(SO4)] and [Cu(C5H11N3S)(2-pic)2(CH3COO)2] were active against S. aureus. Against E. coli, [Zn(C5H11N3S)(2- pic)2(SO4)] showed activity at 18-20 mg dose range.

Synthesis and antibacterial activity of benzyl-[3-(benzylamino-methyl)-cyclohexylmethyl]-amine derivatives.

A series of benzyl-[3-(benzylamino-methyl)-cyclohexylmethyl]-amine derivatives with different substitution pattern on the aromatic ring have been prepared and evaluated for their antibacterial activity against Gram-positive and Gram-negative bacterial strains. Most of the compounds exhibit potent activity against Pseudomonas aeruginosa and Staphylococcus epidermidis while compounds 6l and 6m showed antibacterial activity against all the four bacterial strains with MIC values ranging from 0.002 to 0.016 microg/mL and no hemolytic activity up to 512 microg/mL in mammalian erythrocytes was observed.

In Vitro and Ex Vivo Efficacy of Novel Trp-Arg Rich Analogue of α-MSH against Staphylococcus aureus.

Antimicrobial peptides (AMPs), an essential component of innate immunity, are very important resources for human therapeutics to counter the current threat of drug resistance. We have previously established that one such AMP, α-melanocyte stimulating hormone (α-MSH), an endogenous neuropeptide, and its derivatives have potent antimicrobial activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). However, the immense potential of α-MSH for therapeutic development against staphylococcal infections is marred by its reduced efficacy in the presence of standard microbiological culture medium. To overcome this issue, in this study, we designed a series of five novel analogues of the C-terminal fragment of α-MSH, i.e., α-MSH(6-13), by replacing uncharged and less hydrophobic residues with tryptophan and arginine to increase the hydrophobicity and cationic charge of the peptide, respectively. While all of the peptides showed a preferential interaction with negatively charged phospholipid vesicles, the most hydrophobic and cationic peptide, i.e., Ana-5, exhibited the highest activity against S. aureus cells while maintaining cell selectivity. Moreover, Ana-5 could retain its activity even in complex media like the Mueller Hinton broth and displayed rapid bactericidal activity in the presence of serum. Ana-5 also caused rapid bacterial membrane depolarization, permeabilization, and cell lysis and was able to bind to polyanionic plasmid DNA suggesting a possible dual mode of action of the peptide. Importantly, Ana-5 was able to eradicate intracellular S. aureus in fibroblast cells similar to conventional antibiotics. Collectively, in the present study, we obtained a potent α-MSH-based analogue with excellent staphylocidal potency in microbial growth medium and ex vivo efficacy, which may translate into therapeutic application.

Pb2+ and Cd2+ recovery from water using residual tea waste and SiO2@TW nanocomposites.

This work reports the fabrication of SiO2@TW nanocomposites and their application for Pb2+ and Cd2+ ions sequestration from simulated water. Residual tea waste has also been used for metal ions sequestration to compare the potential of SiO2@TW nanocomposites. The SEM, TEM, BET, FTIR and EDX techniques were employed for the characterization of SiO2@TW nanocomposites and residual tea waste. Particle sizes of SiO2@TW nanocomposites was in the range of 6.8-12 nm. The experiments were carried out in batch mode to explore the effect of various operating parameters on the sequestration of Pb2+ and Cd2+ ions from water. The experimental data was subjected to various thermodynamic, kinetic and isothermic models. According to Langmuir model, the maximum adsorption efficiency of the SiO2@TW nanocomposites was 153 mg/g for Pb2+ and 222 mg/g for Cd2+ but maximum adsorption efficiency of residual tea waste for Pb2+ was 125 mg/g and for Cd2+ was 142.9 mg/g. This study suggested that due to the presence of active sites SiO2@TW nanocomposites has greater potential for metal sequestration than residual tea waste.

Withdrawal Notice: Computational Druglikeness Assessment, Synthesis, Characterization and In vitro Biological Activity Evaluation of some Novel Mixed Metal Complexes of 2-(butan-2-ylidene) Hydrazinecarbothioamide

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