Antimicrobial Studies and Characterization of Copper Surfactants Derived from Various Oils Treated at High Temperatures by P.D.A. Technique

Introduction:Biologically potent compounds are one of the most important classes of materials for the upcoming generations. Increasing number of microbial infectious diseases and resistant pathogens create a demand and urgency to develop novel, potent, safe and improved variety of antimicrobial agents. This initiates a task for current chemistry to synthesize compounds that show promising activity as therapeutic agents with lower toxicity. Therefore, a substantial research is needed for their discovery and improvement. Chemistry of present era aims to build a pollution free environment. For the same, it targets to create some alternativeswhich are eco-friendly and nature loving. Present research work is a step towards achieving such alternatives.Method:For this the metallic soaps of copper (derived from common edible oils) were synthesized. The synthesized copper soaps have been confirmed by elemental analysis, UV, and IR spectroscopic technique. The fungicidal activities of copper soaps derived from soyabean, sesame oils have been evaluated by testing against Alternaria alternate and Aspergillus niger by P.D.A. technique.Result:The fungi toxicity results indicate that the strain of fungal species are susceptible towards these soaps and suggests that with the increase in concentration of copper soap it may increase further. The transition metallic soaps showed good antifungal activity because chelation increases the anti-microbial potency.

Biocidal Activities of Substituted Benzothiazole of Copper Surfactants over Candida albicans & Trichoderma harziamunon on Muller Hinton Agar

Background: Heterocyclic complexes in the current era are aimed at evaluating as new products that possess wide biological, pharmacological, agricultural, medicinal, industrial applications and many more highly significant uses. Although they have been known from long ago for their great biocidal significance, still the researchers pay a great attention for profiling the pharmacological view of novel macrocycles like benzothiazoles. Increasing number of microbial infectious diseases and resistant pathogens create a demand and urgency to develop novel, potent, safe and improved variety of antimicrobial agents. Objective: This initiates a task for current chemistry to synthesize compounds that show promising activity as therapeutic agents with lower toxicity. It is very necessary to introduce new and biologically safe and active drugs eco-friendly in nature and effective as antimicrobial agents. Methods: Transition metal complexes share an important place in this regards. Therefore in this paper we report the synthesis and characterization of transition metal complex of N/S ligand by FT-IR, NMR, ESR, elemental analysis, conductometric and magnetic moment measurements. The synthesized metal complexes were successfully investigated for biological activities namely antifungal. Results: Based on the results we pronounced biocidal activities of the novel complexes. Concerned complexes contribute diverse applications by being more economical, harmless, non -toxic and eco-environmental friendly.

Computational Studies on Imidazo[1,2-a] Pyridine-3-Carboxamide Analogues as Antimycobacterial Agents: Common Pharmacophore Generation, Atom-based 3D-QSAR, Molecular dynamics Simulation, QikProp, Molecular Docking and Prime MMGBSA Approaches

Background: IMB-1402, Q203 and ND09759 analogs were found to have strong efficiency against Multi-drug-resistant tuberculosis (MDR-TB)/Extensively drug-resistant tuberculosis (XDR-TB) strains. Objectives: To know the structural necessities for imidazo[1,2-a]pyridine-3-carboxamide analogues, we intended to develop the ligand-based pharmacophore, Quantitative structure–activity relationship models(3D-QSAR model). We also performed Molecular docking, molecular simulation and Prime/Molecular Mechanics Generalized Born Surface Area (Prime/MM-GBSA) studies. Methods: All the studies like Common pharmacophore hypothesis generation, Atom based 3D-QSAR study, Prime MMGBSA, Docking, Qikprop, and Molecular dynamics simulation were processed using various modules incorporated within the maestro software interface from Schrodinger, LLC, New York USA (release 2017). Results: The common pharmacophore hypothesis(CPH) generation resulted in a five-featured hypothesis HHPRR, containing 1 positive, 2 hydrophobic and 2 aromatic rings. An Atom-based 3D-QSAR model was predicted for twenty seven training sets (a correlation coefficient i.e.R2= 0.9181,Standard deviation i.e.SD =0.3305, variance ratio i.e. F = 85.9) and eleven test sets (cross-validation correlation coefficient i.e.Q2 =0.6745, Root Mean Square Error i.e. RMSE = 0.65, Pearson R = 0.8427, P=1.21E-12) compounds employing alignment based on CPH. The dataset of thirty-eight molecules was allowed for docking into the active site of pantothenate synthetase (PDBID-3IVX) that shows H-bonding (Hydrogen bonding) interactions with residues Gly158, Met195, Pro38 and additionally shows further Pi-cation interactions with a residue like Hie47. We also obtained good simulation results for1.2ns study. Conclusion: From the results, the generated 3D-QSAR model may be applicable for additional designing of various novel potent derivatives in the future.

Antifungal Activities and Characterization of Some New Environmentally Safe Cu (II) Surfactants Substituted 2-Amino-6-Methyl Benzothiazole

Background:Biologically potent compounds are one of the most important classes of materials for the upcoming generations.Objectives:Increasing number of microbial infectious diseases and resistant pathogens create a demand and urgency to develop novel, potent, safe and improved variety of antimicrobial agents.Methods:The copper surfactants substituted 2-amino-6-methyl benzothiazole were synthesized. The synthesized complexes have been characterized by IR, NMR, ESR spectroscopic methods. The antifungal activities have been evaluated by testing againstAlternaria alternatefungi. All complexes showed good antifungal activity because chelation increases the anti-microbial potency.Result:The studies suggest that the copper (II) ions in soaps may be responsible for the enhancement of the activity against fungi. The evaluation of anti -fungal studies further revealed that fungitoxicity of the complexes also depends on the nature of metal ions. The chelation reduces the polarity of central metal ion mainly because of partial attaining of its positive charge with the donor groups and possible π- electron delocalization over the whole chelate ring. Such chelation increases the lipophilic character of the central atom, which subsequently favors its permeation through the lipoid layer of the cell membrane. Their efficiency increases with their concentration.

Improvement in Dissolution of Bosentan Monohydrate by Solid Dispersions Using Spray Drying Technique

Background: Bosentan monohydrate (BM), a dual endothelin receptor antagonist, is indicated for the treatment of patients with pulmonary arterial hypertension (PAH). It is poorly soluble in water, and having absolute bioavailability of 50%. Objective: The aim of the present work is to develop and evaluate the solid dispersions (SD) of a poorly water soluble drug bosentan monohydrate (BM). Method: Solid dispersions (SDs) systems of BM were prepared with Hydroxy propyle β-cyclodextrin (HPβ-CD) and Polyethylene glycol (PEG-4000) polymers using a spray drying technique. Result: The significant rise in a saturation solubility 174.23±1.36 mg/mL; and drug dissolution 95.11±1.22%; was observed with optimized formulation (SD 6). The solid state characterization of optimized formulation (SD 6) by SEM, DSC, and XRPD revealed the absence of crystalline nature of BM in solid dispersion. High dissolution rate of solid dispersion (SD 6) compared with pure drug indicated the increase in dissolution characteristics. Conclusion: In conclusion, our studies illustrated that spray drying technique could be useful large scale producing method to prepare the solid dispersion of bosentan with HP β-CD, which can improve the solubility as well as stability of the formulation.

High Performance Liquid Chromatography (HPLC) Stability Indicating Method for the Determination of Bromazepam Via its Copper (II) Chelates

Introduction: Bromazepam is hydrolyzed in acidic aqueous solution leading to a series of degradation products. The rate of acidic hydrolysis is believed to be dependent on the state of protonation of the pyridyl and azomethine nitrogen atoms. Stability test is important in pharmaceutical industry to provide evidence on how the quality of an active substance or pharmaceutical product varies with time under the influence of a variety of environmental factors. Objective: The aim of the study was to develop a simple stability indicating method for the determination of bromazepam. Method: Bromazepam solution was prepared and forced degradation of bromazepam was performed under acid hydrolysis using sulphuric acid. High performance liquid chromatography determination of pure and degraded bromazepam and bromazepam-copper (II) complex was performed using reversed phase octyl C-8 column under isocratic conditions and the chromatographic conditions were set as follows; the flow rate of the mobile phase was 1.5 mL/min; injection volume was 10 μL, column temperature was 30oC and the detector wavelength being 309 nm. Results: Bromazepam, its degradation product and bromazepam chelated with copper (II) were determined using the developed mobile phase with flow rate of 1.5 mL/min. Good separation with sharp peak, minimum tailing and retention time repeatability was obtained. The rate order, rate constant and half-life of degradation were also determined, and it was observed that the degradation reaction follows the first order kinetics. Conclusion: Chromatographic separation of bromazepam chelated with copper (II) was achieved and the method can be further used in drug manufacturing quality control.

New Insight into Progesterone-dependent Signalization

Background: Various effects of steroid hormone activity cannot easily be explained by the action of classical nuclear receptors and genomic signal transduction pathways. These activities are manifested principally as rapid processes, lasting from seconds to minutes, resulting in changes in ion transduction, calcium intracellular concentration, and level of the second messengers, which cannot be realized through the genomic pathway. Hence, it has been proposed that other kinds of mediators should be involved in steroid-induced processes, namely receptors located on the cell surface. The search for their chemical nature and role is of utmost importance. Current state of knowledge confirms their relation to GPCRs. Moreover, it seems that almost every nuclear receptor specific for steroid hormone family has its membrane-bound equivalent. Objective: In this review, we summarize current state of knowledge about nuclear and membrane receptors for progesterone, and describe their potential functions alone, as well as in cooperation with other receptors. Conclusion: In the light of common expression, both in species and organs, membrane receptors could play a role that is at least comparable to nuclear receptors. Further exploration of membrane receptor-dependent signaling pathways could give a new insight in the treatment of many endocrine and oncological pathologies.

Nanomedicine-Mediated Combination Drug Therapy in Tumor

Background:Combined chemotherapy has gradually become one of the conventional methods of cancer treatment due to the limitation of monotherapy. However, combined chemotherapy has several drawbacks that may lead to treatment failure because drug synergy cannot be guaranteed, achievement of the optimal synergistic drug ratio is difficult, and drug uptake into the tumor is inconsistent. Nanomedicine can be a safe and effective form of drug delivery, which may address the problems associated with combination chemotherapy.Objective:This review summarizes the recent research in this area, including the use of nanoparticles, liposomes, lipid-polymer hybrid nanoparticles, and polymeric micelles, and provides new approach for combined chemotherapy.Methods:By collecting and referring to the related literature in recent years.Results:Compared with conventional drugs, nanomedicine has the following advantages: it increases bioavailability of poorly soluble drugs, prolongs drug circulation timein vivo, and permits multiple drug loading, all of which could improve drug efficacy and reduce toxicity. Furthermore, nanomedicine can maintain the synergistic ratio of the drugs; deliver the drugs to the tumor at the same time, such that two or more drugs of tumor treatment achieve synchronization in time and space; and alter the pharmacokinetics and distribution profilein vivosuch that these are dependent on nanocarrier properties (rather than being dependent on the drugs themselves).Conclusion:Therefore, nanomedicine-mediated combination drug therapy is promising in the treatment of tumors.

Water Soluble Chitosan Mediated Voriconazole Microemulsion as Sustained Carrier for Ophthalmic Application: In vitro/Ex vivo/In vivo Evaluations

Background: Voriconazole (VCZ) is a lipophilic candidate, effective against fungal infections like ocular keratitis and endopthalmitis. Objective: The purpose to develop, optimize and characterize voriconazole microemulsion as sustained medication for ophthalmic application. Methods: The pseudo-ternary phase diagrams were developed using oleic acid, isopropyl myristate and isopropyl palmitate (oil phases), tween 80 (surfactant), propylene glycol (co-surfactant), distilled water (aqueous phase) and modified chitosan (Mod.CH) as mucoadhesive polymer. The optimum composition of oil, Smix and water was selected on the basis of phase diagrams and as mucoadhesive polymer Mod.CH was used in the formulations. All the formulations were evaluated for thermodynamic stability/dispersibility, physicochemical parameters (droplet size, polydispersity index, zeta potential, drug content, viscosity, pH and conductivity), in vitro, ex vivo and in vivo studies. Results: All formulations showed droplet size below 250 nm, positive zeta potential and polydispersity index below 0.5. The in vitro drug release study performed on selected formulations showed maximum sustained release than marketed formulation. The in vitro transcorneal permeation experiment of formulations suggests that optimized formulations showed better permeation. The selected formulation of voriconazole microemulsion was able to produce maximum antifungal activity against Candida albicans when compared to marketed formulation. In vivo study performed on rabbit eyes, found more drug concentration in aqueous humor of optimized formulation; the AUC0→t of IPMVM-11 was approximately 6.84-fold higher than VOZOLE and efficiently enhanced the corneal bioavailability. Conclusion: The modified chitosan based on voriconazole loaded microemulsion was promising novel carrier for sustained action in ophthalmic medication.

Anticonvulsant Activities of 4-benzylidene-6-(4-methyl-phenyl)-4,5-dihydropyridazin-(2H)-ones and 4-benzylidene-6-(4-chloro-phenyl)-4,5-dihydropyridazin-(2H)-ones

Background: Two series of 4-benzylidene-6-(4-methyl-phenyl)-4,5-dihydropyridazin-(2H)-one compounds (3a-e) and 4-benzylidene-6-(4-chloro-phenyl)-4,5-dihydropyridazin-(2H)-ones (3f-j) were synthesized and evaluated as anticonvulsant agents. Methods: Synthesized compounds (3a-3j) were tested against maximum electro shock (MES) and Isoniazid (INH) induced convulsion methods for anticonvulsant activities and neurotoxicity. Results: In MES induced convulsions, result found that the compounds 3e and 3j exhibited highest anticonvulsant activities. In INH induced convulsions, result was indicated that all the compounds exhibited good anticonvulsant activities., whereas compounds 3d and 3j showed maximum activity. Methyl derivatives were more active than chloro derivatives. Phenytoin sodium (25mg/kg) and sodium vaproate (50mg/kg) were used as reference drugs. All these synthesized pyridazinone compounds (3a-j) did not exhibit any neurotoxicity up to 100 mg/kg dose levels. Conclusion: All compounds showed good anticonvulsant activities against both MES and INH induced convulsion models. Many such explorations are anticipated in the near future.