Phytochemical investigation and characterisation of methanolic extract of Glycine max seeds using LCMS/MS and in silico studies for wound healing activity.

Soybean is scientifically known as Glycine max. It belongs to the Fabaceae family. It consists of a lot of bioactive phytochemicals like saponin, phenolic acid, flavonoid, sphingolipids and phytosterols. It also owns excellent immune-active effects in the physiological system. Soy and its phytochemicals have been found to have pharmacological properties that include anticancer, antioxidant, anti-hypercholesterolaemic, anti-diabetic, oestrogenic, anti-hyperlipidaemic, anti-inflammatory, anti-obesity, anti-hypertensive, anti-mutagenic, immunomodulatory, anti-osteoporotic, antiviral, hepatoprotective, antimicrobial, goitrogenic anti-skin ageing, wound healing, neuroprotective and anti-photoageing activities. Present study has been designed to set standard pharmacognostical extraction method, complexation of compounds, qualitative evaluation through phytochemical screening, identification by TLC, physicochemical properties, solubility profile, total phenolic, flavonoid content as well as analytical evaluation or characterisation like UV and FT-IR of methanolic extract of G. max. The final observations like physicochemical properties such as total ash value, LOD and pH were recorded. Phytochemical screenings show the presence of flavonoid, alkaloid, saponin, carbohydrate, tannins, protein, gums and mucilage, fixed oils and fats. The results were found significant. Further in silico studies proved creatinine and euparin to be potent wound healing agents.

Synthesis, spectroscopic analysis, and computational-based investigations on 'azo-coumarin-Co(II)-galangin' hybrids exhibit multipotential activities.

The present study synthesized a series of cobalt (II) metal ion frame hybrid candidates (6a-6f) bearing phyto-flavonol galangin with substituted aryl diazenyl coumarins, and further structural confirmation was validated by various spectral techniques, including NMR, ATR-FTIR, UV-vis, HPLC, XRD, etc. Therapeutic potency was investigated via PASS (prediction of activity spectra for substances), molecular docking, molecular dynamics simulation, prediction of toxicity, pharmacokinetics, and drug-likeness scores, along with the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), with their energy gaps (ΔEH-L) to locate the most potential therapeutic candidates. The PASS prediction (Pa > Pi score) showed that proposed metal complexes have kinase inhibitors, antioxidative, and antischistosomal activities with potential molecular docking scores (> -7 kcal/mol) against selected targeted enzymes. Further, the MD-simulation (RMSD, RMSF, Rg, and H-bonds) of the most potential docking complex, 'HER2-6d', showed a minimum deviation similar to the standard drug (lapatinib) at 100 ns, indicating that 6d could be a potential noncovalent anticancer inhibitor. In addition, metal complexes possess a non-toxic and ideal drug-ability profiles, and positive electron space in an excited state increases the binding affinity towards target enzymes. Among all six ligands, 6c and 6d were the two most multipotent therapeutic agents from the above analyses. In summary, this could be a feasible approach towards the utilization of phytochemicals in mainstream therapeutic applications, where bioinformatics tools help to select a lead drug candidate at an early stage and guide for higher experimental success by proceeding with potential candidates.Communicated by Ramaswamy H. Sarma.

Coumaryl-sulfonamide moiety: Unraveling their synthetic strategy and specificity toward hCA IX/XII, facilitating anticancer drug development.

Currently, cancer is the most grieving threat to society. The cancer-related death rate has had an ascending trend, despite the implementation of numerous treatment strategies or the discovery of an array of potent molecules against several pathways of cancer growth. The need of the hour is to prevent the multidrug resistance toll, and the current efforts have been bestowed upon a versatile small molecule scaffold, coumarin (benz[α]pyrone), a natural compound possessing interesting affinity toward the cancer target human carbonic anhydrase (hCA), focusing on hCA I, II, IX, and XII. Along with coumarin, the age-old known antibacterial drug sulfonamide, when conjugated at positions 3, 7, and 8 of coumarin either with a linker group or as a single entity, has been reported to enhance the affinity of coumarin toward the overexpressed enzymes in tumor cell lines. The sulfonamides have been listed as obsolete drugs due to the severe side effects caused by them; however, their affinity toward the hCA-zinc-binding core has attracted the attention of researchers. Hence, in the process of drug development, coumarin and sulfonamides have remained the choice of last resort. To unveil the synthetic strategy of coumarin-sulfonamide conjugation, their rationale for inhibiting cancer cells/enzymes, and their affinity toward various types of carcinoma have been the sole goal of the researchers. This review specifically focuses on the mechanism of action and the structure-activity relationship through synthetic strategies and the binding affinity of coumaryl-sulfonamide conjugates with the anticancer targets possessing the highest enzyme affinity, since 2008.

Molecules with versatile biological activities bearing antipyrinyl nucleus as pharmacophore.

Antipyrine (1,2-dihydro-1,5-dimethyl-2-phenylpyrazole-3-one) in a structural frame consists of a five membered lactam pyrazolone heterocyclic ring as a pharmacophore moiety. It is evident from literature that the molecules having nitrogen bearing heterocyclic nuclei clearly exhibit several biological actions. Commercially available pyrazolone derivatives as drugs, analgin and metamizol are an established chemical class of analgesics. Recent trends of synthetic routes and several biological actions of antipyrine analogues are considered in this review. Indeed, the synthesized derivatives possess antipyrine moiety having versatile biological properties, antimicrobial, antitubercular, anthelmintic, antioxidant, analgesic, anti-inflammatory, cytotoxic and antiviral activities.

Molecular docking and simulation study for synthesis of alternative dapsone derivative as a newer antileprosy drug in multidrug therapy.

Leprosy (causative, Mycobacterium leprae) continues to be the persisting public health problem with stable incidence rates, owing to the emergence of dapsone resistance that being the principal drug in the ongoing multidrug therapy. Hence, to overcome the drug resistance, structural modification through medicinal chemistry was used to design newer dapsone derivative(s) (DDs), against folic acid biosynthesis pathway. The approach included theoretical modeling, molecular docking, and molecular dynamic (MD) simulation as well as binding free energy estimation for validation of newly designed seven DDs, before synthesis. Theoretical modeling, docking, and MD simulation studies were used to understand the mode of binding and efficacy of DDs against the wild-type and mutant dihydropteroate synthases (DHPS). Principal component analysis was performed to understand the conformational dynamics of DHPS-DD complexes. Furthermore, the overall stability and negative-binding free energy of DHPS-DD complexes were deciphered using Molecular Mechanics/Poisson-Boltzmann Surface Area technique. Molecular mechanics study revealed that DD3 possesses higher binding free energy than dapsone against mutant DHPS. Energetic contribution analysis portrayed that van der Waals and electrostatic energy contributes profoundly to the overall negative free energy, whereas polar solvation energy opposes the binding. Finally, DD3 was synthesized and characterized using Fourier-transform infrared spectroscopy, UV, liquid chromatography-mass spectrometry, and proton nuclear magnetic resonance techniques. This study suggested that DD3 could be further promoted as newer antileprosy agent. The principles of medicinal chemistry and bioinformatics tools help to locate effective therapeutics to minimize resources and time in current drug development modules.

Systematic approach for the formulation and optimization of atorvastatin loaded solid lipid NANOAPARTICLES using response surface methodology.

Atorvastatin is a lipid lowering agent with poor oral bioavailability (12%) because of poor solubility and extensive first pass hepatic metabolism. In order to overcome these issues, atorvastatin loaded solid lipid nanoparticles (ATOR-SLNs) were prepared by using glyceryl tripalmitate as lipid carrier, poloxamer 407 as surfactant and soya lecithin as emulsifier. The purpose of this work was to optimize the formulation with the application of response surface methodology to improve the physicochemical properties. The central composite rotatable design consisting of three factored factorial design with three levels was used for the optimization of the formulations. The optimized formulation was composed of drug/lipid ratio of 1:3.64, surfactant concentration of 1.5% with 5 min time for sonication. Fourier transforms infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies confirmed the compatibility of drug and lipid in the formulation. The optimized ATOR- SLNs showed almost spherical shape with a mean particle size of 338.5 nm, zeta potential of -24.7mV, DL of 17.7% and EE of 81.06% respectively. The in vitro drug release study showed a burst release at the initial stage followed by the prolongation of drug release from lipid matrix. Stability study revealed that ATOR-SLNs were more stable at 4±2˚C when compared with storage at 25±2˚C/60±5% RH during the six months storage period. These results indicated that the developed ATOR-SLNs is a promising approach for increment of bioavailability by improving the physicochemical properties.

Biological investigation of novel metal complexes of 2-amino-4-substituted phenylthiazole Schiff bases.

OBJECTIVE: Invasive microorganisms and free radicals are responsible for the delayed healing of various infections. It is necessary to discovery of novel molecules that are effective against invasive microorganisms and inhibit free radicals. Therefore, a series of metal complexes of 2-amino-4-substituted phenylthiazole Schiff bases were synthesized. METHODS: Structural characterization of the synthesized molecules was performed by elemental analysis, FT/IR, 1H NMR, UV-Vis spectrophotometry, LC-MS, XRD, and SEM. The antimicrobial activities of all the synthesized molecules were investigated by an agar well diffusion method. An acute oral toxicity study of the synthesized ligands and their metal complexes was conducted according to OECD guidelines. The DPPH assay was used to evaluate the radical-scavenging activities of the compounds. RESULTS: Results of the oral acute toxicity study revealed that the synthesized analogues are safe up to a dose of 2000 mg/kg body weight. The complexes bis[{4-((4-bromo-3-methylphenyl)diazenyl)-2-((4-phenylthiazol-2-ylimino)methyl)phenoxy}]cobalt (6a) and bis[4-{(4-bromo-3-methylphenyl)diazenyl}-2-{(4-(4-chlorophenyl)thiazol-2-ylimino)methyl}phenoxy]cobalt (6d) exhibited significant antibacterial activities against drug-resistant bacterial strains as well as potent radical-scavenging properties. CONCLUSION: The results justify that the chelation of metals with Schiff base ligands enhances their biological activities against drug-resistant microbial strains.

Antimicrobial activity of novel synthesized coumarin based transitional metal complexes.

OBJECTIVES: To synthesize new transitional metal complexes derived from 3-aryl-azo-4-hydroxy coumarin analogues and to evaluate their antimicrobial activities. METHODS: The syntheses of complexes of coumarin analogues were accomplished by mixing a hydro-alcoholic solution of 3-aryl-azo-4-hydroxy coumarin analogues with transition metal chlorides. The structural environment of the synthesized molecules was characterized using different instrumental methods. The antimicrobial activity of the compounds was determined by the agar well diffusion method. RESULTS: The cobalt complexes of (E)-3-((4-chlorophenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL1): (4a) and (E)-3-((4-methoxyphenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL2): (4e) showed excellent antimicrobial activities compared with their ligands. CONCLUSION: The reports of the antimicrobial investigation showed that the cobalt complexes of 3-aryl-azo-4-hydroxy coumarin analogues exhibited potential antimicrobial activity that was stronger than that of their ligands.