Green Synthesis, Multitargeted Molecular Docking and ADMET Studies of Chalcones Based Scaffold as Anti-Breast Cancer Agents
Research Journal of Pharmacy and Technology
Green synthesis of chalcones is a new alternative to traditional methods, which is eco-friendly a... more Green synthesis of chalcones is a new alternative to traditional methods, which is eco-friendly and require no solvents. The chalcones exert their anticancer action by the different mechanisms by acting through various targets. The study aimed to synthesise chalcones by green chemistry approach using grinding technique and check their molecular interactions and pharmacokinetic profile by in silico studies. Their anti-breast cancer action was analysed by MTT assay against human breast cancer cells. ADMET and physicochemical properties emphasised the drug-likeness and bioavailability of the synthesised chalcones. All the twelve synthesised chalcones interacted well with the three cancer targets (3ERT, 4OAR and 4WKQ). Among them, the top chalcones were PR2 and PR3, excellently interacting with the targets, which are following the in vitro studies. PR2 and PR3 have obtained good cytotoxic action against human breast cancer cells. Based on these results, it is concluded that the synthesi...
The success or failure of a potential drug depends on its absorption, distribution, metabolism, e... more The success or failure of a potential drug depends on its absorption, distribution, metabolism, excretion and toxicity (ADMET) characteristics, and these features are usually rate-limiting in the drug development process. Hence, it is essential to know about the predicted ADMET properties of the most promising leads to avoid the risk of late-stage attrition. This project focuses on in silico screening of ADMET properties of phytochemicals found in Dakshina Kannada's medicinal plants, which include Tinospora cordifolia, Azadirachta indica, Ocimum sanctum, and Plectranthus amboinicus, mainly known for their antimicrobial properties.The physicochemical properties, bioactivity scores, ADMET, and molecular interactions of the selected phytoconstituents were determined by QikProp, Molinspiration, ADMETlab 2.0, ProTox-II, and GLIDE. In addition, molecular docking checked for their binding interactions with target proteins 1JIJ and 4 HOE of Staphylococcus aureus and Candida albicans, re...
A series of novel Azetidinone derivatives have been synthesized from the intermediate schiff base... more A series of novel Azetidinone derivatives have been synthesized from the intermediate schiff bases. Schiff bases are prepared from sulfamethoxazole moiety by reacting the hydrazide of the parent compound with different aromatic aldehydes. Cyclocondensation of schiff's bases with acetylchloride resulted in the formation of azetidinone derivatives. The products, characterized on the basis of satisfactory spectral data (IR, NMR, Mass spectroscopy), have shown moderate to good antimicrobial activity against some bacteria and fungi.
A series of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives (5... more A series of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives (5a-5v) has been synthesized and confirmed by physicochemical(R f , melting point) and spectral means (IR, 1 HNMR, 13 CNMR). The results of in vitro antidiabetic study against α-glucosidase indicated that compound 5o bearing 2-CH 3-5-NO 2 substituent on phenyl ring was found to be the most active compound against both enzymes. The electron donating (CH 3) group and electron withdrawing (NO 2) group on a phenyl ring highly favoured the inhibitory activity against these enzymes. The docking simulations study revealed that these synthesized compounds displayed hydrogen bonding, electrostatic and hydrophobic interactions with active site residues. The structure activity relationship studies of these compounds were also corroborated with the help of molecular modeling studies. Molecular dynamic simulations have been done for top most active compound for validating its α-glucosidase and α-amylase inhibitory potential, RMSD analysis of ligand protein complex suggested the stability of top most active compound 5o in binding site of target proteins. In silico ADMET results showed that synthesized compounds were found to have negligible toxicity, good solubility and absorption profile as the synthesized compounds fulfilled Lipinski's rule of 5 and Veber's rule.
International Journal of Applied Pharmaceutics, Apr 27, 2019
Objective: Present study is aimed at formulation of Hydrogel containing Poly Lactic Glycolic Acid... more Objective: Present study is aimed at formulation of Hydrogel containing Poly Lactic Glycolic Acid (PLGA) nanoparticles incorporated with ethanolic extract of Crossandra infundibuliformis (EECI) and investigate the efficacy of hydrogel nanoparticles as a carrier of antimicrobial constituents. Methods: Poly Lactic Glycolic Acid (PLGA) nanoparticles containing ethanolic extract of Crossandra infundibuliformis (EECI) were synthesized by an emulsion-evaporation method and their physicochemical properties were studied. Polymeric PLGA nanoparticles were then incorporated into gel matrix, using Hydroxy Propyl Methyl Cellulose (HPMC K4M) as a base. The antibacterial activity of nanoparticulated hydrogel formulations were evaluated by agar well diffusion method against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa. Results: Nanoparticulate hydrogel formulations exhibited high viscosity, neutral pH with good spreadability which is appropriate for transdermal application as well as showed prolonged drug release from optimized formulation up to 24 h. Nanoparticulate hydrogel formulations were effective inhibitors of all the microorganisms with more promising activity against Staphylococcus aureus. Conclusion: Nanoparticulate hydrogel formulation can be used as a feasible alternative to conventional formulations of Crossandra infundibuliformis extract with advanced permeation characteristics of antimicrobial constituents for transdermal application.
Journal of pharmaceutical research international, Apr 7, 2021
Drug resistance causes serious difficulties in the routine therapy for curing common microbial in... more Drug resistance causes serious difficulties in the routine therapy for curing common microbial infections. Thus it is very essential to develop new antimicrobial agents which can offer alternative treatments. The development of potent and effective antimicrobial agents is of utmost importance to overcome the emerging multidrug resistance strains of bacteria and fungi. The technique involves Knoevenagel reaction between substituted salicylaldehyde and ethyl acetoacetate in presence of piperidine as catalyst to give 3-acetyl coumarin. The intermediate coumarinyl chalcones was synthesized by condensing with various substituted benzaldehyde in presence of ethanolic KOH. The final synthesized pyridine-3-carbonitrile derivative was prepared upon refluxing with coumarinyl chalcones with malononitrile in presence of ammonium acetate. All the newly synthesized Original Research Article
Diabetes is a chronic hyperglycemic disorder that leads to a group of metabolic diseases. This co... more Diabetes is a chronic hyperglycemic disorder that leads to a group of metabolic diseases. This condition of chronic hyperglycemia is caused by abnormal insulin levels. The impact of hyperglycemia on the human vascular tree is the leading cause of disease and death in type 1 and type 2 diabetes. People with type 2 diabetes mellitus (T2DM) have abnormal secretion as well as the action of insulin. Type 2 (non-insulin-dependent) diabetes is caused by a combination of genetic factors associated with decreased insulin production, insulin resistance, and environmental conditions. These conditions include overeating, lack of exercise, obesity, and aging. Glucose transport limits the rate of dietary glucose used by fat and muscle. The glucose transporter GLUT4 is kept intracellular and sorted dynamically, and GLUT4 translocation or insulin-regulated vesicular traffic distributes it to the plasma membrane. Different chemical compounds have antidiabetic properties. The complexity, metabolism, ...
Benzimidazole derivatives occupied an important part in medicinal chemistry because of their mult... more Benzimidazole derivatives occupied an important part in medicinal chemistry because of their multifarious therapeutic actions. Inflammation is a protective response involving immune cells, blood vessels and molecular mediators. The key enzyme required for the conversion of arachidonic acid to prostaglandins is cyclooxygenase (COX). The two isomers of this enzyme are COX-1 and COX-2 and inhibiting this enzyme is very crucial in alleviating inflammation. The present study has performed an in silico analysis to determine the inhibitory effect of some synthesized benzimidazoles on COX enzymes, which were previously reported for their anti-inflammatory activity. The physicochemical and ADMET properties were determined by qikprop application of Schrodinger. The molecular docking studies of the synthesised benzimidazole derivatives with active protein sites was performed by docking program, Glide and pharmacophore model was developed by phase module of Schrodinger. All the synthesized comp...
Background: Trigonella foenum-graecum (fenugreek) seeds are reported to contain multiple antidiab... more Background: Trigonella foenum-graecum (fenugreek) seeds are reported to contain multiple antidiabetic constituents and hence widely used for the treatment of diabetes mellitus. The present investigation was aimed to formulate capsule formulations containing crude extract of fenugreek seeds in order to obtain antidiabetic formulations with more effective oral hypoglycemic activity, less side effects, increased patient compliance thereby providing multifaceted benefits. Methodology: Capsule formulations were prepared by encapsulation of granules prepared from the fenugreek seed extract with various concentration of sodium starch glycolate as superdisintegrant (0-5%). Finished capsule formulations were evaluated for weight variation, disintegration time, drug content (trigonelline) content, in vitro-drug release, in vivo antidiabetic activity studies. Results: Fenugreek capsule formulations pass the test for weight since the percentage deviation of individual weight of capsule from mean were found within ±7.5%. Drug (trigonelline) content of all the formulations were more than 85%. Disintegration time ranged from 7-15 mins. Dissolution profile showed 77.06-90% drug release in phosphate buffer of pH 6.8 after 6 hours. Antidiabetic activity studies of capsules significantly (p≤ 0.001) reduced blood glucose level in diabetic rats after 15 days of treatment when compared to diabetic control group. Conclusion: From the results, we concluded that formulation of fenugreek seed extracts into suitable and appropriate herbal dosage form may be more desirable, advantageous and therapeutically more beneficial than incorporating the direct plant materials for the treatment of diabetes.
Objective: Present study is aimed at formulation of hydrogel containing PLGA nanoparticles loaded... more Objective: Present study is aimed at formulation of hydrogel containing PLGA nanoparticles loaded with of Crossandra infundibuliformis (CI) extract. Leaf extract of Crossandra infundibuliformis has been reported to possess antibacterial, antifungal activity hence an attempt was done to improve the efficacy of the extract by formulating into nanoparticulate hydrogel which can be used as a feasible alternative to conventional formulations of Crossandra infundibuliformis extract with dual benefit of sustained release and advanced permeation characteristics for transdermal application. Methodology: In this study, the active ingredients present in the leaves of Crossandra infundibuliformis (CI) were extracted by cold maceration using ethanol. The crude extracts were developed into polymeric nanoparticles by nanoprecipitation method using PLGA as polymer, polyvinyl alcohol as surfactant and dimethyl sulphoxide as organic phase solvent. Polymeric nanoparticles were incorporated into gel matrix containing HPMC K4M as gel matrix base. Results: Polymeric nanoparticles showed nearly spherical shape with z-average 143-325nm, PDI in the range of 0.235-0.299 and-2.08 mV to-3.58mV zeta potential with maximum % drug entrapment of 69%. Nanoparticulate hydrogel formulations showed high viscosity, neutral pH with good spreadability which is suitable for transdermal application. In vitro drug release showed initial burst release of 28.56 ± 0.93 % with prolonged drug release of 90.06± 0.93 % from optimized formulation up to 24 h. Conclusion: Nanoparticulate hydrogel can be used as carrier for transdermal delivery of extract of Crossandra infundibuliformis.
Objective: The aim of the present study was to formulate and optimize the PLGA polymeric nanopart... more Objective: The aim of the present study was to formulate and optimize the PLGA polymeric nanoparticle of Nebivolol Hydrochloride for sustain release of drug Methods: The drug-excipients interaction was explored by molecular docking studies by in silico tools. The drug-loaded polymeric nanoparticles prepared by emulsion solvent evaporation method using 32 factorial design and characterized for particle size, zeta potential, and entrapment efficiency. Shape and surface morphology was analysed by SEM and TEM. In vitro drug release study was performed by using a diffusion membrane. Results: The docking analysis inferred that the drug has interacted well with PLGA and PF-68, which could prevent the drug crystal formation. The optimized polymeric nanoparticles had a particle size of 291 nm and entrapment efficiency of 83.4% and were found to be within 95% of CI of the predicted value, which is acceptable. SEM and TEM studies showed that the formed polymeric nanoparticles were smooth, sphe...
Uploads
Papers by jainey james