Department Of Pharmaceutical Sciences and Natural Products

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Author: search.filters.author.Bhatia, NehaHas files: No

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    Developing our knowledge of the quinolone scaffold and its value to anticancer drug design
    (Taylor and Francis Ltd., 2023-08-18T00:00:00) Singh, Yogesh; Bhatia, Neha; Biharee, Avadh; Kulkarni, Swanand; Thareja, Suresh; Monga, Vikramdeep
    Introduction: The quinolone scaffold is a bicyclic benzene-pyridinic ring scaffold with nitrogen at the first position and a carbonyl group at the second or fourth position. It is endowed with a diverse spectrum of pharmacological activities, including antitumor activity, and has progressed into various development phases of clinical trials for their target-specific anticancer activity. Areas covered: The present review covers both classes of quinolones, i.e. quinolin-2(H)-one and quinolin-4(H)-one as anticancer agents, along with their possible mode of binding. Furthermore, their structure-activity relationships, molecular mechanisms, and pharmacokinetic properties are also covered to provide insight into their structural requirements for their rational design as anticancer agents. Expert opinion: Synthetic feasibility and ease of derivatization at multiple positions, has allowed medicinal chemists to explore quinolones and their chemical diversity to discover newer anticancer agents. The presence of both hydrogen bond donor (?NH) and acceptor (-C=O) functionality in the basic scaffold at two different positions, has broadened the research scope. In particular, substitution at the -NH functionality of the quinolone motif has provided ample space for suitable functionalization and appropriate substitution at the quinolone�s third, sixth, and seventh carbons, resulting in selective anticancer agents binding specifically with various drug targets. � 2023 Informa UK Limited, trading as Taylor & Francis Group.
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    Elacestrant: a new FDA-approved SERD for the treatment of breast cancer
    (Springer, 2023-05-16T00:00:00) Bhatia, Neha; Thareja, Suresh
    Elacestrant (RAD-1901), a selective estrogen receptor degrader, was approved by USFDA on January 27, 2023, for the treatment of breast cancer. It has been developed by Menarini Group under the brand name Orserdu�. Elacestrant showed anticancer activity both in vitro and in vivo in ER+ HER2-positive breast cancer models. The present review delebrates the development stages of Elacestrant, with its medicinal chemistry, synthesis, mechanism of action, and pharmacokinetic studies. Clinical data and safety profile has also been discussed, including data from randomized trials. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Selective Estrogen receptor degraders (SERDs) for the treatment of breast cancer: An overview
    (Elsevier Masson s.r.l., 2023-05-04T00:00:00) Bhatia, Neha; Hazra, Shreejita; Thareja, Suresh
    Discovery of SERDs has changed the direction of anticancer research, as more than 70% of breast cancer cases are estrogen receptor positive (ER+). Therapies such as selective estrogen receptor modulators (SERM) and aromatase inhibitors (AI's) have been effective, but due to endocrine resistance, SERDs are now considered essential therapeutics for the treatment of ER+ breast cancer. The present review deliberates the pathophysiology of SERDs from the literature covering various molecules in clinical trials. Estrogen receptors active sites distinguishing characteristics and interactions with currently available FDA-approved drugs have also been discussed. Designing strategy of previously reported SERDs, their SAR analysis, in silico, and the biological efficacy have also been summarized along with appropriate examples. � 2023 Elsevier Masson SAS
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    Molecular docking, 3D-QSAR and simulation studies for identifying pharmacophoric features of indole derivatives as 17?-hydroxysteroid dehydrogenase type 5 (17?-HSD5) inhibitors
    (Taylor and Francis Ltd., 2023-02-06T00:00:00) Kulkarni, Swanand; Singh, Yogesh; Biharee, Avadh; Bhatia, Neha; Monga, Vikramdeep; Thareja, Suresh
    Excess of androgens leads to various diseases such as Poly-Cystic Ovarian Syndrome, Prostate Cancer, Hirsutism, Obesity and Acne. 17?-Hydroxysteroid Dehydrogenase type 5 (17?-HSD5) converts androstenedione into testosterone peripherally, thereby significantly contributing to the development of these diseases. Indole-bearing scaffolds are reported as potential 17?-HSD5 inhibitors for the manifestation of diseases arising due to androgen excess. In the present work, we have extensively performed a combination of molecular docking, Gaussian field-based 3D-QSAR, Pharmacophore mapping and MD-simulation studies (100 ns) to identify the pharmacophoric features of indole-based compounds as potent 17?-HSD5 inhibitors. Molecular simulation studies of the most potent compound in the binding pocket of enzyme revealed that the compound 11 was stable in the binding pocket and showed good binding affinity through interactions with various residues of active site pocket. The Molecular mechanics Generalized Born surface area continuum solvation (MM/GBSA) and Molecular mechanics Poisson�Boltzmann surface area (MM/PBSA) calculations revealed that the compound 11 possessed a free binding energy of ?36.36 kcal/mol and ?7.00 kcal/mol, respectively, which was better as compared to reference compound Desmethyl indomethacin (DES). The developed pharmacophore will be helpful to design novel indole-based molecules as potent 17?-HSD5 inhibitors for the treatment of various androgenic disorders. Communicated by Ramaswamy H. Sarma. � 2023 Informa UK Limited, trading as Taylor & Francis Group.
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    Recent Advancements in the Discovery of MDM2/MDM2-p53 Interaction Inhibitors for the Treatment of Cancer
    (Bentham Science Publishers, 2022-11-16T00:00:00) Bhatia, Neha; Khator, Rakesh; Kulkarni, Swanand; Singh, Yogesh; Kumar, Pradeep; Thareja, Suresh
    Discovery of MDM2 and MDM2-p53 interaction inhibitors changed the direction of anticancer research as it is involved in about 50% of cancer cases globally. Not on-ly the inhibition of MDM2 but also its interaction with p53 proved to be an effective strategy in anticancer drug design and development. Various molecules of natural as well as synthetic origin have been reported to possess excellent MDM2 inhibitory potential. The present review discusses the pathophysiology of the MDM2-p53 interaction loop and MDM2/MDM2-p53 interaction inhibitors from literature covering recent patents. Focus has also been put on characteristic features of the active site of the target and its desired interactions with the currently FDA-approved inhibitor. The designing approach of previ-ously reported MDM2/MDM2-p53 interaction inhibitors, their SAR studies, in silico studies, and the biological efficacy of various inhibitors from natural as well as synthetic origins are also elaborated. An attempt is made to cover recently patented MDM2/MD-M2-p53 interaction inhibitors. � 2023 Bentham Science Publishers.