Browsing by Author "Chaudhary, Hema"

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    A Deep Dive into PDE5 Inhibition: Innovative Discoveries via Virtual Screening
    (Bentham Science Publishers, 2024) Debnath, Abhijit; Chaudhary, Hema; Sharma, Parul; Singh, Rajesh; Srivastava, Shikha
    Background: PDE5 inhibitors have had a surge in popularity over the last decade owing to their efficacy in the treatment of erectile dysfunction, coronary vasculopathy, and pulmonary arterial hypertension. These inhibitors exhibit competitive binding with phosphodiesterase type 5 and inhibit the hydrolysis of cyclic guanosine monophosphate, hence elevating the levels of cGMP in smooth muscle cells and prolonging the duration of an erection. However, due to production costs and side effects, further research is needed to discover new PDE5 inhibitors. Objectives: The study aimed to identify potent PDE5 inhibitors by employing the extensive application of computer-aided drug design. Methods: Three different databases, named Million Molecules Database, Natural Product Database, and NCI Database, have been screened, which has been followed by filtering based on various drug-likeness rules, docking, ADME, toxicity, consensus molecular docking, and 100 ns molecular dynamics simulation. Results: Three compounds (ZINC05351336, ZINC12030898, and ZINC17949426) have exhibited stable-binding characteristics at the active site of PDE5, demonstrating a robust binding affinity. These molecules have been found to possess drug-like capabilities, effective ADME features, low toxicity, and high stability. Conclusion: The study has delved into the realm of PDE5 inhibitors, which have been found to be effective in treating erectile dysfunction, but high production costs and side effects necessitate new ones. Through computer-aided drug design and screening, three compounds have been identified with promising binding characteristics, drug-appropriate properties, effective ADME profiles, mini-mal toxicity, and stability, making them potential candidates for future PDE5 inhibitors. © 2024 Bentham Science Publishers.
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    Discovery of Novel Cathepsin D Inhibitors by High-Throughput Virtual Screening
    (AMG Transcend Association, 2023) Debnath, Abhijit; Chaudhary, Hema; Kumar, Rajesh; Shokeen, Ankit; Khurana, Riya
    Cathepsin D (CatD) is a cancer-associated inflammation protein that plays an important role in cancer-associated inflammation, osteoarthritis, and various neurodegenerative diseases. CatD is genetically stable and does not easily develop drug resistance. Targeting CatD is an interesting strategy for both cancer therapy and cancer prevention. Thus, we have tried working on CatD as a therapeutic target in this research. To identify potent CatD inhibitors, we have screened the Million Molecules Database, Natural Product Database, and NCI Database. Top hits have been filtered based on various drug-likeness rules, followed by ADME profiling, toxicity prediction, and Consensus Molecular docking. Our research work resulted in three molecules: ZINC12198861 (-9.6 Kcal/mol), ZINC2438311 (-9.5 kcal/Mol), and ZINC14533276 (-8.9 kcal/mol) are stability-binding at the active site of CatD with strong binding affinity, drug-like properties, effective ADME properties, low toxicity, and high stability. Inhibiting CatD with these identified molecules will promote apoptosis and cure cancer-associated inflammation and osteoarthritis. © 2023 by the authors.
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    Discovery of Novel PTP1B Inhibitors by High-throughput Virtual Screening
    (Bentham Science Publishers, 2025) Debnath, Abhijit; Rani, Anjna; Mazumder, Rupa; Mazumder, Avijit; Singh, Rajesh Kumar; Sharma, Shalini; Srivastava, Shikha; Chaudhary, Hema; Mishra, Rashmi; Khurana, Navneet; Sanchitra, Jahanvi; Jan, Sk Ashif
    Aim: To Discover novel PTP1B inhibitors by high-throughput virtual screening Background: Type 2 Diabetes is a significant global health concern. According to projections, the estimated number of individuals affected by the condition will reach 578 million by the year 2030 and is expected to further increase to 700 million deaths by 2045. Protein Tyrosine Phosphatase 1B is an enzymatic protein that has a negative regulatory effect on the pathways involved in insulin signaling. This regulatory action ultimately results in the development of insulin resistance and the subsequent elevation of glucose levels in the bloodstream. The proper functioning of insulin signaling is essential for maintaining glucose homeostasis, whereas the disruption of insulin signaling can result in the development of type 2 diabetes. Consequently, we sought to utilize PTP1B as a drug target in this investigation. Objective: The purpose of our study was to identify novel PTP1B inhibitors as a potential treatment for managing type 2 diabetes. Methods: To discover potent PTP1B inhibitors, we have screened the Maybridge HitDiscover database by SBVS. Top hits have been passed based on various drug-likeness rules, toxicity predictions, ADME assessment, Consensus Molecular docking, DFT, and 300 ns MD Simulations. Results: Two compounds have been identified with strong binding affinity at the active site of PTP1B along with drug-like properties, efficient ADME, low toxicity, and high stability. Conclusion: The identified molecules could potentially manage T2DM effectively by inhibiting PTP1B, providing a promising avenue for therapeutic strategies. © 2024 Bentham Science Publishers.
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    Quest for discovering novel CDK12 inhibitor
    (Taylor and Francis Ltd., 2025) Debnath, Abhijit; Singh, Rajesh Kumar; Mazumder, Rupa; Mazumder, Avijit; Srivastava, Shikha; Chaudhary, Hema; Mangal, Saloni; Sanchitra, Jahanvi; Tyagi, Pankaj Kumar; Kumar Singh, Sachin; Singh, Anil Kumar
    CDK12 is essential for cellular processes like RNA processing, transcription, and cell cycle regulation, inhibiting cancer cell growth and facilitating macrophage invasion. CDK12 is a significant oncogenic factor in various cancers, including HER2-positive breast cancer, Anaplastic thyroid carcinoma, Hepatocellular carcinoma, prostate cancer, and Ewing sarcoma. It is also regarded as a potential biomarker, emphasizing its broader significance in oncology. Targeting CDK12 offers a promising strategy to develop therapy. Various monoclonal antibodies have drawn wide attention, but they are expensive compared to small-molecule inhibitors, limiting their accessibility and affordability for patients. Consequently, this research aims to identify effective CDK12 inhibitors using comprehensive high-throughput virtual screening. RASPD protocol has been employed to screen three different databases against the target followed by drug-likeness, molecular docking, ADME, toxicity, Consensus molecular docking, MD Simulation, and in-vitro studies MTT assay. The research conducted yielded one compound ZINC11784547 has demonstrated robust binding affinity, favorable ADME features, less toxicity, remarkable stability, and cytotoxic effect. The identified compound holds promise for promoting cancer cell death through CDK12 inhibition. © 2024 Informa UK Limited, trading as Taylor & Francis Group.