Pharmaceutical Sciences and Natural Products - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/56

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Author: search.filters.author.Thareja, SureshSubject: search.filters.subject.Breast cancer

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Now showing 1 - 8 of 8
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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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    Medicinal chemistry aspects and synthetic strategies of coumarin as aromatase inhibitors: an overview
    (Springer, 2022-12-05T00:00:00) Ratre, Pooja; Kulkarni, Swanand; Das, Sweety; Liang, Chengyuan; Mishra, Pradyumna Kumar; Thareja, Suresh
    Coumarin is a bicyclic oxygen bearing heterocyclic scaffold formed by fusion of benzene with the pyrone ring. Because of its unique physicochemical characteristics and the ease with which it may be transformed into a wide range of functionalized coumarins during�synthesis, coumarin provides a privileged scaffold for medicinal chemists. As a result, many coumarin derivatives have been developed, synthesized, and evaluated to target a variety of therapeutic domains, thereby making it an attractive template for designing novel anti-breast cancer compounds. The main culprit in estrogen overproduction in the estrogen-dependent breast cancer (EDBC), is the enzyme aromatase (AR), and it is thought to be a significant target for the effective treatment of EDBC. Considering coumarins versatility, this review presents a detailed overview of diverse study of aromatase as a target for coumarins. An overview of structure�activity relationship analysis of coumarin core is also included so as to summarize the desired pharmacophoric features essential for design and development of aromatase inhibitors (AIs) using coumarin core. Identification of key synthesis techniques that could aid researchers in designing and developing novel analogues with significant anti-breast cancer properties along with their mechanism of action have also been covered in the current review. Graphical Abstract: [Figure not available: see fulltext.] � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Selective Estrogen Receptor Modulators (SERMs) for the treatment of ER+ breast cancer: An overview
    (Elsevier B.V., 2022-08-02T00:00:00) Das, Sweety; Kulkarni, Swanand; Singh, Yogesh; Kumar, Pradeep; Thareja, Suresh
    Breast cancer is a major threat to women's lives throughout the world. Hormone-dependent or estrogen-receptor positive (ER+) breast cancer accounts for more than 80% of all instances. Selective Estrogen Receptor Modulators (SERMs), which specifically control the ERs and limit the progression of breast malignancy, have drawn the interest of researchers in the treatment of breast cancer by regulation of the estrogen receptors (ER), particularly ER?. The mode of action, anti-proliferative potential, SAR, and favourable interactions of the potent candidates are elaborated. Many potent SERMs with diversity in structural space have been rationally designed and reported in the literature for their anti-breast cancer activity. These SERMs exhibited remarkable anti-proliferative activity against ER+ BC. Since, ER? is responsible for the initiation and progression of BC, there is an urgent need to strategically design and synthesize new SERMs, having more selective binding towards ER?. Long term use of traditionally marketed SERMs is associated with several adverse effects, such as development of endometrial cancer and other disorders. Insight of structural features in the present review will prove to be a guideline for the researchers to design and develop potent SERMs for the treatment of ER+ breast cancer. � 2022 Elsevier B.V.
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    De novo designing, assessment of target affinity and binding interactions against aromatase: Discovery of novel leads as anti-breast cancer agents
    (Springer, 2020-11-13T00:00:00) Verma, Sant Kumar; Ratre, Pooja; Jain, Akhlesh Kumar; Liang, Chengyuan; Gupta, Ghanshyam Das; Thareja, Suresh
    Aromatase inhibitors (AIs) have been emerged as promising anti-cancer agents for the treatment of hormone dependent breast cancer (HDBC) in women because of their excellent ability of inhibiting oestrogen synthesis. Here, we have implicated structure-based comprehensive approaches to discover novel drug/lead-like AIs. The molecular modelling and energy optimization were performed using Chem Office package. The e-LEA3D web server was used to design novel drug/lead-like AIs as well as generation of ADME/drug-likeness parameters. Target binding affinities and mode of binding interactions were mapped using Molegro Virtual Docker (MVD) to re-optimize the best de novo generated molecules. We have successfully designed novel AIs (compounds 1�7) using de novo technique performed on e-LEA3D. All the designed molecules were found optimum drug-like candidates based on various in silico screening parameters including �rule of five�. The energy optimized conformers of generated molecules (1�7) were docked in the active site, corresponding to co-crystallized androstenedione (ASD), of aromatase to predict ligand-target binding affinity and their binding interactions. The molecules (1�7) showed comparable to higher binding affinity towards aromatase with MolDock Score ranges from ? 134.881 to ? 152.453�Kcal/mol as compared with natural substrate ASD (? 128.639�Kcal/mol) and standard letrozole (? 136.784�Kcal/mol). The de novo designed molecules (1�7) can be developed as novel AIs, and their binding properties can be used for the further designing of newer AIs by medicinal chemists. � 2020, Springer Science+Business Media, LLC, part of Springer Nature.
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    In silico docking of anti cancerous drugs with ?-cyclodextrin polymer as a prominent approach to improve the bioavailability
    (Bentham Science Publishers, 2020-10-14T00:00:00) Jain, Akhlesh K.; Mishra, Keerti; Thareja, Suresh
    Background: ?-Cyclodextrin, a cyclic oligosaccharides having 7 macrocyclic rings of glucose subunits usually linked together by ?-1,4 glycosidic bond, bears characteristic chemical structure, with an exterior portion as hydrophilic to impart water solubility and interior cavity as hydrophobic, for hosting the hydrophobic molecules. Objective: In the present work binding affinities and interactions between various anti-cancerous drugs and ?cyclodextrin using molecular docking simulations was examined for the bioavailability enhancement of cytotoxic drugs through improved solubility for the treatment of breast cancer. Methods: Molegro Virtual Docker, an integrated software was used for the prediction and estimation of interaction between ?-cyclodextrin and anti cancerous drugs. Results: Out of tested anti cancerous drug, Olaparib having pyridopyridazione scaffold possess highest MolDock (-130.045) and Re-ranks score (-100.717), ensuring strong binding affinity. However, 5-Fluoro Uracil exhibited the lowest MolDock score (-61.0045), indicating weak or no binding affinity, while few drugs showed no H-bond interaction with the ?-cyclodextrin. Conclusion: The binding conformations of anti cancerous drugs obtained from the present study can be selected for the development of improved formulation having superior solubility which will lead to attain better pharmacological profile with negligible toxicity. � 2021 Bentham Science Publishers.
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    Polymeric nanoparticles of aromatase inhibitors: A comprehensive review
    (Bentham Science Publishers, 2020-09-29T00:00:00) Mishra, Keerti; Ratre, Pooja; Thareja, Suresh; Jain, Akhlesh K.
    Being the second most frequent cancer, breast cancer is emerging worldwide with an alarming rate, specifically in post-menopausal women. Targeted drug delivery has been in the focus for the successful treatment of breast cancer by enhancing the drug delivery efficiency and reducing the systemic toxicity of drugs. Al-so, it eliminates the drawbacks associated with conventional chemotherapy, including neuropathy, memory loss, cardiotoxicity and low RBCs count. This review elaborates the polymeric nanoparticles based formulation approaches for selective and sustained delivery for effective cure of breast cancer. However, breast cancer, a life-threatening disease, is mostly caused because of estrogen, thus aromatase inhibitors and estrogen synthesis inhibitors could prevent chances of breast cancer. The disease is associated with drug resistance and some side effects, which could be easily eliminated by using novel therapeutic approaches. Aromatase inhibitors, when en-trapped in nanoparticles, have shown sustained drug release, advocating themselves to be beneficial for the treatment of breast cancer. � 2021 Bentham Science Publishers.
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    In silico molecular interaction studies of chitosan polymer with aromatase inhibitor: Leads to letrozole nanoparticles for the treatment of breast cancer
    (Bentham Science Publishers, 2020-08-26T00:00:00) Mishra, Keerti; Verma, Sant K.; Ratre, Pooja; Banjare, Laxmi; Jain, Abhishek; Thareja, Suresh; Jain, Akhlesh K.
    Background: It takes a lot more studies to evaluate the molecular interaction of nanoparticles with the drug, their drug delivery potential and release kinetics. Thus, we have taken in silico and in vitro approaches into account for the evaluation of the drug delivery ability of the chitosan nanoparticles. Objective: The present work was aimed to study the interaction of chitosan nanoparticles with appropriate aromatase inhibitors using in silico tools. Further, synthesis and characterization of chitosan nanoparticles having optimal binding energy and affinity between drug and polymer in terms of size, encapsulation efficiency were carried out. Methods: In the current study, molecular docking was used to map the molecular interactions and estimation of binding energy involved between the nanoparticles and the drug molecules in silico. Letrozole is used as a model cytotoxic agent currently being used clinically; hence Letrozole loaded chitosan nanoparticles were formulated and characterized using photomicroscope, particle size analyzer, scanning electron microscope and fourier transform infra-red spectroscopy. Results: Letrozole had the second-highest binding affinity within the core of chitosan with MolDock (-102.470) and Re-rank (-81.084) scores. Further, it was investigated that formulated nanoparticles were having superior drug loading capacity and high encapsulation efficiency. In vitro drug release study exhibited prolonged release of the drug from chitosan nanoparticles. Conclusion: Results obtained from the in silico and in vitro studies suggest that Letrozole loaded nanoparticles are ideal for breast cancer treatment. � 2021 Bentham Science Publishers.