DESIGN, SYNTHESIS, AND DOCKING OF SULFADIAZINE SCHIFF BASE SCAFFOLD FOR THEIR POTENTIAL CLAIM AS INHA ENOYL-(ACYL-CARRIER-PROTEIN) REDUCTASE INHIBITORS

Objective: An effort was made to design and synthesize the series of sulfadiazine building blocks as a targeted candidate for antimycobacterial activity.Method: The synthesized compounds were subjected to preliminary in silico screening study for testing their antimycobacterial action by doing their molecular docking study on bioinformatics software, molecular operating environment 2009.10.Result: The results obtained from this tool showed that there is a best docking affinity score of these target compounds against the enzyme InhA Enoyl-(acyl-carrier-protein) reductase from Mycobacterium tuberculosis (MTB) pathogen, which is one of the key enzymes involved in the type II fatty acid biosynthesis pathway of MTB.Conclusion: Thus, the synthesized sulfadiazine Schiff base derivatives might serve as the best drug candidate for the existence of menacing pathogen MTB.Â

SYNTHESIS, EVALUATION AND DOCKING STUDIES OF NOVEL FORMAZAN DERIVATIVES AS AN ENOYL-ACP REDUCTASE INHIBITORS

Objective: To synthesize, evaluate and performing the docking studies of novel formazan derivatives as enoyl-ACP reductase inhibitors.Materials: In the present investigation, a series of formazans (Ia-d) were synthesized by stirring aryl diazonium salts solution with Schiff's base at 0-5˚C for 2 h. The intermediate azomethine (Schiff base) itself was synthesized by condensation of para aminobenzoic acid with dimethylamino benzaldehyde in presence of a glacial acetic acid as a catalyst. The antimicrobial activity was done for these synthesized compounds by cup plate method. Moreover, the antimicrobial activity was further confirmed by its molecular docking approach study by using Molecular Operating Environment (MOE) 2009.10 software.Results: In the present study all the synthesized compounds (Ia-Id) showed the enhanced zone of inhibition against S. aureus, B. subtilis, E. coli and S. typhi (5±0.12 to 12±0.45) whereas, the antifungal activity against A. niger and C. albicans were showed the zone of inhibition in the range of 9±0.51 to 12±0.43 when compared to that of the standard drug.Further the docking study reveals that, only three of the formazan compounds under observation (Ia, Ib and Ic) have higher binding affinity with the receptors enzymes enoyl-ACP reductase, which is in the narrow range of binding energy for the protein PDB: 1C14 is-24.4598 to-23.9377 kcal/mol, which shows the further confirmation of these formazan compounds as better microbial inhibitor.Conclusion: Therefore our present report shows that formazans could be the potential drug candidate that inhibits the microbial activity by interacting and inhibiting the enoyl-ACP reductase enzyme which is confirmed by its both in vitro antimicrobial study and as well as from its docking study

SYNTHESIS, BIOLOGICAL EVALUATION, AND DOCKING STUDY OF NOVEL 2-PHENYL-1- BENZOPYRAN-4-ONE DERIVATIVES - AS A POTENT CYCLOOXYGENASE-2 INHIBITOR

Objective: The inflammation and oxidative stress were related together in the generation of reactive oxygen species, which is responsible for the enhancement of inflammation associated with various chronic diseases. Methods: The aim of this study is to synthezise and characterizes the flavones (2-phenyl-1-benzopyran-4-one) derivatives and analyzed by their docking hypothetical data as an effective anti-inflammatory mediator against cyclooxygenase-2 (COX-2) enzyme. Further, the evaluation of various in vitro antioxidant and anti-inflammatory studies was carried out. Results: The 10 compounds were synthesized and characterized by ultraviolet, infrared, nuclear magnetic resonance, and mass spectroscopic techniques. The docking data results of these 10 flavones derivatives against COX-2 enzymes (Protein Data Bank ID: 3LN1) showed the binding energy ranging between −5.53 kcal/mol and −7.02 kcal/mol when compared with that of the standard diclofenac (−6.34 kcal/mol). The in vitro studies suggest that the lipophilic character of the side chain donor, along with the hydroxyl substituted flavones found to have significant half maximal inhibitory concentration values. Conclusion: Based on these in silico and in vitro evaluation results, these synthesized compounds could act as a promising inhibitor to target the COX- 2 enzyme. Hence, those compounds were effective in the management of chronic diseases by exhibits free radical scavenging and anti-inflammatory property

DEVELOPMENT AND PHYSICO-CHEMICAL EVALUATION OF MONOLITHIC MATRIX TYPE TRANSDERMAL FILMS OF AMMONIA METHACRYLATE COPOLYMER-METHOCEL AND METHACRYLIC ACID COPOLYMER-METHOCEL OF A MODEL ANTI-HYPERTENSIVE DRUG

The main challenge of the present study is to effectively design a Monolithic Matrix type of transdermal films with the use of binary blends of polymers (Methacrylic Acid Copolymer: Acrylcoat S100 & Acrylcoat L100-Methocel K15M and Ammonia Methacrylate Copolymer: Eudragit RSPO & Eudragit RLPO-MK15M and use of most appropriate plasticizer: hydrophilic such as Polyethylene glycol 400 & Propylene Glycol or hydrophobic such as Dibutyl phthalate (DBT) & Dibutyl sebacate for that particular combination of polymers so that a good film can be obtained. In this research work, 2 different permeation enhancers of Terpene class such as d- limonene and 1,8 cineole in combination were used. The Physico-chemical properties of patches determined for the suitability and acceptability of the prepared patches. The thickness, weight, tensile strength, % elongation, folding endurance and flatness were determined for the prepared patches. We found good and acceptable Physicochemical parameters of the matrix films regarding properties and performance. Keywords: Transdermal, Monolithic, Matrix films, Physico-chemical propertie

Antihyperglycemic activity of Trichosanthes tricuspidata root extract

To evaluate the anti-diabetic activity of ethanolic extract of Trichosanthes tricuspidata root in alloxan induced diabetic rats and to perform the phytochemical screening. The extraction, preliminary phytochemical screening, anti-diabetic activity in alloxan induced diabetic rats  by oral administration of  extract (200 and 400 mg/kg b.w.), the blood glucose level and biochemical parameters like cholesterol, triglyceride, serum protein, SGPT, SGOT, and ALP were estimated. Phytochemical studies shows the presence of carbohy-drates, proteins, glycosides and terpenoids and the ethanolic extract of T. tricuspidata root significantly lowered the blood sugar level. The above findings justified the traditional claim of anti-diabetic activity in this plant

ANTI-OXIDANT AND ANTI-MICROBIAL ACTIVITIES OF SYNTHETIC 3-FORMYL, 7-FLAVONOL INTERMEDIATES OBTAINED BY MICROWAVE ASSISTED TECHNIQUE

Objective: The synthesized compounds of 3-formyl, 7-flavonols*, after characterization, aimed to be tested for their anti-oxidant and anti-microbial activities.Methods: i) anti-oxidant activities by hydrogen peroxide-nitric oxide-and by alkaline DMSO-methods and ii) anti-microbial activities against various gram-negative and gram-positive pathogens and against candida albicans by disc diffusion method.Results: Findings were found to be dose dependent and IC50 value was 30-60 µg/ml and the results revealed that the dinitro-, trinitro-and acetyl, dinitro derivatives showed better and/or equipotent activity to that of the standard, ascorbic acid. The synthesized compounds at a concentration of (1 μg/10 μl/disc) showed variable inhibitory activities against all bacteria with inhibition zone diameters ranging from 7-26 mm and a good antifungal activity against Candida albicans at the concentration of (1 μg/10 μl/disc) with inhibition of 10-24 mm. Klebsiella tribatta are more susceptible to the action of the formylated samples, giving high inhibition values comparing to the other organisms. Compounds Ie and Ih resulted to a higher activity index (AI>1); compounds Id, Ig and Ii showed an equal value (AI=1); whereas, Ia, Ib, Ic and If showed only a moderate activity (AI<1) compared to the standard, Amikacin.Conclusion: The findings confirmed that the synthetic compounds of 3-formyl, 7-flavonol derives have significant anti-oxidant and anti-microbial activities.*Synthesis and characterization work of 3-formyl, 7-flavonols has already been accepted for publication by the journal Elseveir, Procedio Chemistry and is in process.Â

Bactericidal activity of skin mucus and skin extracts of Catla catla and Channa striatus

Fishes counteract certain microbial attacks in water by producing antimicrobial proteins/peptides in their skin surface. The present study focused on screening the bactericidal activity of skin and skin mucus extracts of Catla catla and Channa striatus. The bactericidal activity was assessed against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus vulgaris, Aeromonas hydrophila, Staphylococcus aureus and Bacillus coagulans by disc diff usion method. The minimal inhibitory concentration was also determined. Protein profi les in skin and skin mucus extracts were analyzed by SDS-PAGE. Samples from both fi shes showed antibacterial activity. Detailed analysis of individual protein and peptide would throw light on their medicinal importance to be used against pathogenic microbes

EVALUATION OF BIOACTIVITIES OF MORINDA TINCTORIA LEAVES EXTRACT FOR PHARMACOLOGICAL APPLICATIONS.

 Objective: The present study was aimed to prepare Morinda tinctoria leaves extracts with the different solvent system and to evaluate the bioactivities.Methods: The extracts of M. tinctoria were qualitatively analyzed for the primary phytochemical content. The functional groups of extract were determined by Fourier-transform infrared spectroscopy (FT-IR) analysis. The antimicrobial properties were determined by plate assays. The antioxidant and in vitro anti-inflammatory properties and membrane stabilizing nature of aqueous extract of M. tinctoria (AEM) were measured using a spectrophotometer.Results: The aqueous, ethanolic, and acetone extracts of M. tinctoria were prepared. AEM contains quinones, steroids, terpenoids, phenols, glycosides, and tannins. FTIR result showed that AEM comprises of alkyl halides, 1°, 2° amines, aromatics, aliphatic amines, alcohols, carboxylic acids, esters, ethers, and alkanes, saturated aliphatic, and phenolic groups. The antimicrobial property of M. tinctoria varied based on the solvent used for the extraction. About 86.90±0.36, 78.58±0.13, and 80.33±0.09% of total antioxidant capacity, reducing power, and hydrogen peroxide scavenging activity were observed in AEM, respectively. The 1, 1- diphenyl 2-picrylhyorazyl and 2, 2-Azinobis-(3 ethylbenzothiazoline-6-sulfonic acids) assay results indicated 85.20±0.50 and 52.41±0.60% of free radical scavenging activity in AEM. The protease activity (44.10±0.26%) and protein degradation (44.38±0.58%) were proscribed by AEM. AEM prevents 69.36±0.20% of cell lysis.Conclusion: The results revealed that the AEM leaves were harmless and enriched with potent bioactive principles, which is further used for food and pharmacological applications

DEVELOPMENT AND VALIDATION OF BIOANALYTICAL RP HPLC METHOD FOR THE ESTIMATION OF METOPROLOL TARTRATE IN RABBIT PLASMA AFTER TRANSDERMAL AND ORAL ADMINISTRATION: APPLICATION IN PHARMACOKINETIC STUDIES

A simple, specific, sensitive and rapid Reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for the quantification of Metoprolol Tartrate in small volumes of rabbit plasma. The method was further extended for its pharmacokinetic studies in rabbit plasma samples after transdermal and oral administration. Biological sample preparation involving simple extraction with organic solvent, followed by dilution with mobile phase was adopted to eliminate any chromatographic solvent effects. The method was proven to be linear over a plasma concentration range of 20 ng/ml to100 ng/ml with a mean correlation coefficient of 0.99. The limit of detection and the limit of quantification of the newly developed method were determined to be 5.8ng/mL and 16.1ng/mL, respectively. The method was successfully applied to assess pharmacokinetic parameters of Metoprolol Tartrate in rabbit plasma and found out the comparative bioavailability of MT following oral and transdermal dosage forms. The developed method was established as a rapid analytical tool in a pharmacokinetic study as it required short retention time, high precision, sensitivity and small volumes of plasma for analysis. Keywords: Metoprolol Tartrate, RP-HPLC, quantification, Rabbit plasma, Pharmacokinetic study, oral, transdermal. Â

Bio-inspired computation: where we stand and what's next

In recent years, the research community has witnessed an explosion of literature dealing with the adaptation of behavioral patterns and social phenomena observed in nature towards efficiently solving complex computational tasks. This trend has been especially dramatic in what relates to optimization problems, mainly due to the unprecedented complexity of problem instances, arising from a diverse spectrum of domains such as transportation, logistics, energy, climate, social networks, health and industry 4.0, among many others. Notwithstanding this upsurge of activity, research in this vibrant topic should be steered towards certain areas that, despite their eventual value and impact on the field of bio-inspired computation, still remain insufficiently explored to date. The main purpose of this paper is to outline the state of the art and to identify open challenges concerning the most relevant areas within bio-inspired optimization. An analysis and discussion are also carried out over the general trajectory followed in recent years by the community working in this field, thereby highlighting the need for reaching a consensus and joining forces towards achieving valuable insights into the understanding of this family of optimization techniques