Biology subjects

Ballav, S.

Publications and source records attributed to Ballav, S..

4 recordsLinked to original sources

bioRxiv2025

SieveAI: Development of an Automated extensible and customisable drug discovery pipeline and its validation

Systematic Interaction Evaluation and Virtual Enhancement Analysis Interface (SieveAI) is an automated drug discovery pipeline developed to enhance the efficiency of virtual screening and computer-aided drug discovery processes. The molecular docking workflow encompasses acquiring, modeling, and pre-processing of molecular structure files, conducting docking with various algorithms, and subsequent analysis and interpretation of the outcomes by visualising or tabulating the results. While several open-source software tools are available to assist these operations at different steps of molecular docking, they often necessitate manual user intervention at every stage. To streamline and automate this extensive manual process and develop a comprehensive solution, we have developed an innovative, fully extensible, molecular docking pipeline SieveAI ((C)L-129927/2023). The same has been demonstrated in this manuscript. SieveAI works with a range of open-source libraries, packages, and programs to facilitate automated drug discovery using established programs and software. The package is accessible at https://miRNA.in/SieveAI.

bioinformatics↗

bioRxiv2022

Partial Activation of PPAR-gamma by Synthesized Quercetin Derivatives Modulates TGF-beta-Induced EMT in Lung Cancer cells

Non-small cell lung cancer (NSCLC) possess very low survival rate due to poor response to chemotherapy and late detection. Epithelial to mesenchymal transition (EMT) is regarded as a major contributor to drive metastasis during NSCLC progression. Towards this, transforming growth factor-beta 1 (TGF-{beta}1) is the key driver that endows cancer cells with increased aggressiveness. Recently, our group synthesized a series of Schiff base quercetin derivatives (QDs) and ascertained their effectiveness on EMT markers of A549 cell line. Our study evidenced that EMT process was counteracted via the partial activation of a nuclear hormone receptor, Peroxisome proliferator-activated receptor (PPAR)-{gamma} through QDs. Hence, here we extended our work to investigate the interplay between PPAR-{gamma} partial activation by synthesized QDs, TGF-{beta}1-induced EMT and migration in human lung cancer A549 cells. The results revealed that TGF-{beta}1 played a critical role in suppressing PPAR-{gamma}, which was markedly reversed and increased by partial agonists; QUE2FH and QUESH at both protein and transcriptional level. Compared to full agonists, rosiglitazone could not elevate PPAR-{gamma} expression in the presence of TGF-{beta}1 and had negligible effect on translocation of PPAR-{gamma} to nucleus. The partial agonists not only stimulated PPAR-{gamma} in balanced manner but also prevented the loss of E-cadherin and acquisition of TGF-{beta}1-induced mesenchymal markers (Snail, Slug, Vimentin and Zeb-1). Subsequently, the effects were accompanied by attenuation of TGF-{beta}1-induced migratory ability of A549 cells. Together, with the balanced activation profile of PPAR-{gamma} ligands, our findings suggest that these novel partial agonists may serve as potential anti-cancer agents to impede metastasis.

cancer biology↗

bioRxiv2022

Design, synthesis and biological evaluation of novel quercetin derivatives as PPAR-γ partialagonists by modulating Epithelial-mesenchymal transition in lung cancer metastasis

Epithelial-to-mesenchymal transition (EMT) is responsible for driving metastasis of multiple cancer types including lung cancer. Peroxisome proliferator-activated receptor (PPAR)-{gamma}, a ligand-activated transcription factor, controls expression of variety of genes involved in EMT, cellular differentiation, fatty acid metabolism, insulin sensitivity and adipogenesis. Several synthetic compounds act as potent full agonist for PPAR-{gamma}. However, owing to their serious adverse effects, restricts their long-term application. Therefore, partial agonist has been greatly in demand which involves reduced and balanced PPAR-{gamma} activity. Our previous study discerned the efficacy of quercetin and its derivatives to attain favourable stabilization with PPAR-{gamma}. Here we extended this work by synthesizing five novel quercetin derivatives (QDs) namely thiosemicarbazone (QUETSC) and hydrazones (QUEINH, QUENH, QUE2FH and QUESH) and analysed their effects in modulating EMT of lung cancer cell lines via PPAR-{gamma} partial activation. QDs-treated A549 cells exhibited cell death strongly in a dose and time dependent manner at nanomolar concentration along with anti-migratory effects compared to NCI-H460 cells. Of the five derivatives we screened, QUETSC, QUE2FH and QUESH exhibited the property of partial activation as compared to the over-expressive level of rosiglitazone (RSG). Consistently, with PPAR-{gamma} partial activation, these QDs also suppressed EMT process by markedly down-regulating the levels of mesenchymal markers (Snail, Slug and Zeb-1) and concomitant up-regulation of epithelial marker (E-cadherin). In the light of these evidences; QUETSC, QUE2FH and QUESH could be used as a novel selective partial PPAR-{gamma} modulators whose pharmacological properties is distinct from RSG and may be exploited as potential therapeutic anti-metastatic agent.

cancer biology↗

bioRxiv2019

Enhanced biodegradation of naphthalene by Pseudomonas sp. consortium immobilized in calcium alginate beads

Polycyclic aromatic hydrocarbons (PAHs) belong to a large group of organic pollutant which considers as a potential health hazard to living beings. Herein, naphthalene biodegradation potential by free and immobilized Pseudomonas putida strain KD10 and Pseudomonas sp. consortium were studied. Additionally, naphthalene 1, 2-dioxygenase (nahAc) was sequenced and analyzed, which reveals two altered amino acid residues. However, the altered amino acid residues are not present in the vicinity of the active site. The gas-phase binding free energy ({Delta}GLondon) of the mutant variant of naphthalene 1, 2-dioxygenase was -7.10 kcal mol-1 which closely resembles the wild type variant. Naphthalene biodegradation rate by Pseudomonas putida strain KD10 was 79.12 mg L-1 day-1 and it was significantly elevated up to 123 mg L-1 day-1 by the immobilized Pseudomonas sp. consortium. The half-life (t1/2) for naphthalene biodegradation was 3.1 days with the inhibition constant (ki), substrate saturation constant (ks) and maximum specific degradation rate constant (qmax) of 1268 mg L-1, 395.5 mg L-1 and 0.65 h-1, respectively, for the Pseudomonas putida strain KD10. However, the t1/2 value was significantly reduced to 2 days along with ki, ks and qmaxvalues of 1475 mg L-1, 298.8 mg L-1 and 0.71 h-1, respectively, by the immobilized Pseudomonas sp. consortium. The GC-MS data suggest that KD10 might follow D-gluconic acid mediated meta-cleavage pathway of catechol biodegradation. It is concluded that naphthalene biodegradation performance by immobilized Pseudomonas sp. consortium was superior to free or immobilized Pseudomonas putida KD10. Microbial consortium immobilization could be a useful tool for water quality management and environmental remediation.\n\nHighlightsO_LISuperior naphthalene biodegradation by Pseudomonas sp. consortium immobilized in calcium alginate beads.\nC_LIO_LIA common mutation prone amino acid stretch inside chain A of naphthalene 1, 2-dioxygenase has been identified.\nC_LIO_LIA new naphthalene biodegradation pathway by Pseudomonas putida strain KD10 has been proposed.\nC_LI

microbiology↗