QSAR Study on Thiazolidine-2,4-dione Derivatives for Antihyperglycemic Activity

A set of seventy four molecules belonging to the class of thioglitazones were subjected to the QSAR analysis for their antihyperglycemic activity. All the molecules were subjected to energy minimization to get 3D structures, followed by conformational analysis to get the conformation of the molecule associated with the least energy and highest stability. Various physico-chemical parameters were then calculated using ALCHEMY 2000 software, namely, thermodynamic parameters, structure-dependant parameters, topological parameters and charge-dependant parameters. Multiple linear regression analysis was carried out on all the molecules. The final equation was developed by choosing optimal combination of descriptors after removing the outliers. Cross validation was performed by leave one out method to arrive at the final QSAR model for the chosen set of molecules to exhibit antihyperglycemic activity

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Not AvailableCapripox viruses in the poxviridae family show an emerging worldwide threat to small ruminants. And they cause severe poxviral infection with high mortality and morbidity rates making them potentially useful for economic bioterrorism. This research investigated and evaluated GCMS bioactive compounds from methanolic leaf extract of Leucas aspera by targeting the Capripox viral RNA polymerase and p32 immunogenic proteins using in silico molecular docking approaches with FDA approved drugs. Through GC MS analysis 19 phytochemical compounds were detected in methanolic leaf extracts. Among all five phytochemicals Imidazole 4 2amino1methylethyl n Hexylmethane sulfonamide N E 4 Bromophenyl methylidene 4 methyl benzohydrazide 2 6 Dimethyl benzaldehyde carbamoyl hydrazone methyl N hydroxybenzene carboximidate was accepted as a potent drug like compound through pharmacokinetic. The discovery of antiviral drugs is of immense significance in reducing the incidence of novel poxvirus infections both economically and geographically. Thus the present study may lead to the development of novel Anti Capripox viral drugs using Leucas aspera in the development of herbal medicines for various ailments.Not Availabl

Identification of novel benzimidazole-based small molecule targeting dual targets Tankyrase and Bcl2 to induce apoptosis in Colon cancer

Tankyrase is a crucial protein involved in the regulation of various proteins, among which the Wnt / beta catenin pathway and TERF1 are the main critical pathway proteins. Deregulation of the Wnt / beta catenin pathway has been reported in various cancers. Tankyrase regulates the Wnt / beta catenin pathway by stabilizing AXIN1 and AXIN2 through a proteasomal degradation pathway. Targeting tankyrase is an attractive strategy to target cancer due to the importance of tankyrase in the regulation of TERF1, which is directly involved in the maintenance of telomeric length. Bcl2, another crucial antiapoptotic protein predominantly overexpressed in various cancer types involves cell survival and chemo-resistance. Synthesized compounds have displayed potent antiproliferative activity against various cancer cells specifically HCT116 cells displayed the most sensitivity to compounds with IC50 of 32.9 mu M. The compound induces efficient apoptosis which was unveiled by Annexin V / PI double staining in HCT116 cells. Colony formation capabilities were diminished in the compound treatment group which displays the potent antiproliferative activity of the compound against HCT116 cells. In silico studies displayed strong interaction of compound 5d with Tankyrase and Bc12 with a strong binding score of -6.70 kcal/mol and -6.16 kcal/mol respectively. (C) 2022 Elsevier B.V. All rights reserved

Novel glitazones as PPARγ agonists: molecular design, synthesis, glucose uptake activity and 3D QSAR studies

Abstract Background An alarming requirement for finding newer antidiabetic glitazones as agonists to PPARγ are on its utmost need from past few years as the side effects associated with the available drug therapy is dreadful. In this context, herein, we have made an attempt to develop some novel glitazones as PPARγ agonists, by rational and computer aided drug design approach by implementing the principles of bioisosterism. The designed glitazones are scored for similarity with the developed 3D pharmacophore model and subjected for docking studies against PPARγ proteins. Synthesized by adopting appropriate synthetic methodology and evaluated for in vitro cytotoxicity and glucose uptake assay. Illustrations about the molecular design of glitazones, synthesis, analysis, glucose uptake activity and SAR via 3D QSAR studies are reported. Results The computationally designed and synthesized ligands such as 2-(4-((substituted phenylimino)methyl)phenoxy)acetic acid derivatives were analysed by IR, 1H-NMR, 13C-NMR and MS-spectral techniques. The synthesized compounds were evaluated for their in vitro cytotoxicity and glucose uptake assay on 3T3-L1 and L6 cells. Further the activity data was used to develop 3D QSAR model to establish structure activity relationships for glucose uptake activity via CoMSIA studies. Conclusion The results of pharmacophore, molecular docking study and in vitro evaluation of synthesized compounds were found to be in good correlation. Specifically, CPD03, 07, 08, 18, 19, 21 and 24 are the candidate glitazones exhibited significant glucose uptake activity. 3D-QSAR model revealed the scope for possible further modifications as part of optimisation to find potent anti-diabetic agents

View the PDF document Morphometric Studies of Cytological Specimens in Breast Carcinoma using Computerised Image Analysis System .

The value of nuclear parameters were determined using interactive computer image analysis system on 100 preoperative FNAC smears of breast lesion were radical mastectomy was performed subsequently. Twenty cases of benign lesion were taken as control. The lymph node status was correlated with the nuclear and nucleolar variables. It is found that few nuclear parameters have good discriminatory power. Computerised interactive morphometry proved to be far superior to eye-piece measurements with respect to accuracy, reproducibility and time taken for parameter estimation which leads to the determination of better prognostic indicator

Novel Derivatives of Eugenol as a New Class of PPARγ Agonists in Treating Inflammation: Design, Synthesis, SAR Analysis and In Vitro Anti-Inflammatory Activity

The main objective of this research was to develop novel compounds from readily accessed natural products especially eugenol with potential biological activity. Eugenol, the principal chemical constituent of clove (Eugenia caryophyllata) from the family Myrtaceae is renowned for its pharmacological properties, which include analgesic, antidiabetic, antioxidant, anticancer, and anti-inflammatory effects. According to reports, PPARγ regulates inflammatory reactions. The synthesized compounds were structurally analyzed using FT-IR, 1HNMR, 13CNMR, and mass spectroscopy techniques. Molecular docking was performed to analyze binding free energy and important amino acids involved in the interaction between synthesized derivatives and the target protein. The development of the structure–activity relationship is based on computational studies. Additionally, the stability of the best-docked protein–ligand complexes was assessed using molecular dynamic modeling. The in-vitro PPARγ competitive binding Lanthascreen TR-FRET assay was used to confirm the affinity of compounds to the target protein. All the synthesized derivatives were evaluated for an in vitro anti-inflammatory activity using an albumin denaturation assay and HRBC membrane stabilization at varying concentrations from 6.25 to 400 µM. In this background, with the aid of computational research, we were able to design six novel derivatives of eugenol synthesized, analyzed, and utilized TR-FRET competitive binding assay to screen them for their ability to bind PPARγ. Anti-inflammatory activity evaluation through in vitro albumin denaturation and HRBC method revealed that 1f exhibits maximum inhibition of heat-induced albumin denaturation at 50% and 85% protection against HRBC lysis at 200 and 400 µM, respectively. Overall, we found novel derivatives of eugenol that could potentially reduce inflammation by PPARγ agonism

Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New <i>Serratia marcescens</i> JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of <i>Serratia</i> Species for Biological Applications

Prodigiosin pigment has high medicinal value, so exploring this compound is a top priority. This report presents a prodigiosin bioactive compound isolated from Serratia marcescens JSSCPM1, a new strain. The purification process of this compound involves the application of different chromatographic methods, including UV-visible spectroscopy, high-performance liquid chromatography (HPLC), and liquid chromatography–mass spectrometry (LC/MS). Subsequent analysis was performed using nuclear magnetic resonance (NMR) to achieve a deeper understanding of the compound’s structure. Finally, through a comprehensive review of the existing literature, the structural composition of the isolated bioactive compound was found to correspond to that of the well-known compound prodigiosin. The isolated prodigiosin compound was screened for antibacterial activity against both Gram-positive and Gram-negative bacteria. The compound inhibited the growth of Gram-negative bacterial strains compared with Gram-positive bacterial strains. It showed a maximum minimum inhibitory concentration against Escherichia coli NCIM 2065 at a 15.9 ± 0.31 μg/mL concentration. The potential binding capabilities between prodigiosin and the OmpF porin proteins (4GCS, 4GCP, and 4GCQ) were determined using in silico studies, which are generally the primary targets of different antibiotics. Comparative molecular docking analysis indicated that prodigiosin exhibits a good binding affinity toward these selected drug targets