School Of Basic And Applied Sciences

Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/17

Browse

Author: search.filters.author.Das, AgnidiptaHas files: No

Search Results

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Item
    Identification of 1,3,4-oxadiazoles as tubulin-targeted anticancer agents: a combined field-based 3D-QSAR, pharmacophore model-based virtual screening, molecular docking, molecular dynamics simulation, and density functional theory calculation approach
    (Taylor and Francis Ltd., 2023-09-11T00:00:00) Das, Agnidipta; Sarangi, Manaswini; Jangid, Kailash; Kumar, Vijay; Kumar, Amit; Singh, Praval Pratap; Kaur, Kamalpreet; Kumar, Vinod; Chakraborty, Sudip; Jaitak, Vikas
    Cancer is one of the most prominent causes of death worldwide and tubulin is a crucial protein of cytoskeleton that maintains essential cellular functions including cell division as well as cell signalling, that makes an attractive drug target for cancer drug development. 1,3,4-oxadiazoles disrupt microtubule causing G2-M phase cell cycle arrest and provide anti-proliferative effect. In this study, field-based 3D-QSAR models were developed using 62 bioactive anti-tubulin 1,3,4-oxadiazoles. The best model characterized by PLS factor 7 was rigorously validated using various statistical parameters. Generated 3D-QSAR model having high degree of confidence showed favourable and unfavourable contours around 1,3,4-oxadiazole core that assisted in defining proper spatial positioning of desired functional groups for better bioactivity. A five featured pharmacophore model (AAHHR_1) was developed using same ligand library and validated through enrichment analysis (BEDROC160.9 value = 0.59, Average EF 1% = 27.05, and AUC = 0.74). Total 30,212 derivatives of 1,3,4-oxadiazole obtained from PubChem database was prefiltered through validated pharmacophore model and docked in XP mode on binding cavity of tubulin protein (PDB code: 1SA0) which led into the identification of 11 HITs having docking scores between ?7.530 and ?9.719 kcal/mol while the reference compound Colchicine exerted docking score of ?7.046 kcal/mol. Following the analysis of MM-GBSA and ADME studies, HIT1 and HIT4 emerged as the two promising hits. To verify their thermodynamic stability at the target site, molecular dynamic simulations were carried out. Both HITs were further subjected to DFT analysis to determine their HOMO-LUMO energy gap for ensuring their biological feasibility. Finally, molecular docking based structural exploration for 1,3,4-oxadiazoles to set up a lead of Formula I for further advancements of tubulin polymerization inhibitors as anti-cancer agents. Communicated by Ramaswamy H. Sarma. � 2023 Informa UK Limited, trading as Taylor & Francis Group.
  • No Thumbnail Available
    Item
    Hetero Cyclic Compounds in the Treatment of Triple-Negative Breast Cancer
    (Bentham Science Publishers, 2023-01-02T00:00:00) Mandal, Sudip Kumar; Das, Agnidipta; Bose, Anindya; Dwibedi, Vagish; Ganguly, Paramita; Sarkar, Sipra; Prakash, Ranjana; Dey, Biplab Kumar; Mandal, Sanjeet; Rath, Santosh Kumar
    Triple-negative breast cancer (TNBC) holds just about 15% of all breast tumours and sub-types of breast cancer with distinct characteristics of negative expressions for the progesterone recep-tor, estrogen receptor, and human epidermal growth factor receptor 2. Unfortunately, treatment options for TNBCs are minimal. Most currently available therapies proved inefficient in holding back this aggressive natural treatment of TNBC, in most cases calling for an immediate need for more effective and safer anti-TNBC agents. Based on research reported in recent years, this review pre-sents the report's overview of anti-TNBC compounds and their efficacy, being classified according to the structures. Breast Cancer type 1 and type 2 genes (BRCA1/2) mutations are associated with TNBC. Poly (ADP-Ribose) Polymerases (PARPs) are a family of enzymes involved in numerous cellular processes, including DNA repair. PARP-1 inhibition is involved in the loss of DNA repair via BRCA-dependent mechanisms. PARP-1 inhibitors like Olaparib, Rucaparib, Niraparib, and Tala-zoparib have proved as promising therapeutic medications as monotherapy and in combination with cytotoxic therapy or radiotherapy in various types of cancers. This review is focused on presenting the status of therapeutics against TNBC. The critical spotlight of this review is to encapsulate the versatility and notable success of heterocyclic pharmacophores-based molecules in treating TNBC. � 2023 Bentham Science Publishers.
  • No Thumbnail Available
    Item
    Effectiveness of Selective Estrogen Receptor Modulators in Breast Cancer Therapy: An Update
    (Bentham Science Publishers, 2022-10-06T00:00:00) Das, Agnidipta; Lavanya, Kanamarlapudi Joshna; Nandini; Kaur, Kamalpreet; Jaitak, Vikas
    Background: Breast cancer is considered to be 2nd most common cancer sub-type investigated worldwide. It is mainly prevalent in postmenopausal women. Estrogen Receptor (ER) is a primary transcription factor for the survival and growth of tumors. Around 80% BCs of all classes are ER-positive (ER+). Powerful evidence for estrogen proved to be involved in BC pathogenesis both exogenously and endogenously. It brings the concept of ER inhibitors to treat BC with distinct mechanisms into focus and ER PROTACs (Proteolysis-Targeting Chimeras), AIs (Aromatase inhibitors), SERMs (Selec-tive estrogen receptor modulators), and SERDs (Selective estrogen receptor degrader) were developed. For over 30 years, Tamoxifen, a triphenylethylene SERM, was the drug of choice solely to treat ER+BC patients. Although several SERMs got approval by US FDA after tamoxifen, complicacies remain because of dangerous adverse effects like en-dometrial carcinoma, hot flashes, and VTE (Venous thromboembolism). In addition to that, drug-resistant tumors put a surging need for novel, potent candidates with no or low adverse effects for ER+ BC prevention. Objectives: This article explores the possibilities of SERMs as effective BC agents. Methods: A detailed literature survey of the history and recent advancements of SERMs has been carried out, taking BC as the primary target. This review provides information about ER structure, signaling, pharmacological action, chemical classification with SAR analysis, and benefits and adverse effects of SERMs as potential BC agents. Results: Exhaustive literature studies suggested that SERMs having an agonistic, antago-nistic or mixed activity to ER could efficiently inhibit BC cell proliferation. Conclusion: Each chemical class of SERMs comprises some salient features and poten-tials, which may be further investigated to obtain novel effective SERMs in BC therapy. � 2023 Bentham Science Publishers.