Department of Pharmacy
Permanent URI for this collectionhttp://localhost:4000/handle/123456789/1931
Browse
16 results
Search Results
Item Folic acid-conjugated ferulic acid-entangled single-walled carbon nanotubes: a targeted therapeutic approach for effective breast cancer treatment(Elsevier, 2025-09) Murugesan, SankaranarayananBreast cancer remains one of the major causes of cancer-related deaths in the world for women, which emphasizes the need for better treatment approaches. Conventional therapies target both cancerous as well as normal cells, which can lead to serious adverse effects. This research aimed to develop a targeted therapy employing a new folic acid-conjugated Ferulic Acid-Entangled Single-Walled Carbon Nanotubes (FA-FeA-SWCNTs) formulation to maximize treatment specificity and reduce off-target effects. The efficiency of the FA-FeA-SWCNTs formulation against breast cancer is assessed in this study. Molecular modelling studies were performed to predict the mechanism of action of ferulic acid. FA-FeA-SWCNTs particle size analysis, FTIR, XRD, and SEM were assessed to confirm the formulation tethered to single-walled carbon nanotubes (SWCNTs). MTT assay against MCF-7 cells and CAM assays in chicken eggs were executed to measure cytotoxicity and evaluate anti-angiogenesis efficacy. Sub-acute oral toxicity by OECD 407 guidelines and DMBA-induced breast cancer models in female Wistar rats were used to examine the in vivo anticancer efficacy. The potential therapeutic mechanism was suggested by the study's finding that the Ferulic Acid strongly interacted with mitogen-activated protein kinase (MAPK). The formulation showed excellent-, stability, and suitable particle size. Through in vitro tests, substantial anti-angiogenic effects (71.2 % inhibition) and significant cytotoxicity (IC50 of 19.60 μg/mL) were identified. Subacute toxicity tests verified a favorable safety profile, and in vivo, the formulation successfully decreased tumor growth and improved overall wellness, making it a viable option for more clinical investigation.Item Design, synthesis, graph theoretical analysis and molecular modelling studies of novel substituted quinoline analogues as promising anti-breast cancer agents(Springer, 2022-08) Murugesan, SankaranarayananThe most promising class of heterocyclic compounds in medicinal chemistry are those with the quinolin-2-one nucleus. It is a versatile heterocyclic molecule that has been put together with numerous pharmaceutical substances and is crucial in the creation of anticancer medications. In this view, the present research work deals with design, synthesis, and characterization of various analogous of quinolin-2-one nucleus and evaluation of their anticancer activity against MCF-7 cells (adenoma breast cancer cell line). Fourteen new compounds have been synthesised using suitable synthetic route and are characterized by FTIR, 1H NMR, 13C NMR and Mass spectral data. Molecular docking studies of the title compounds were carried out using PyRx 0.8 tool in AutoDock Vina program. All the synthesised compounds were exhibited well conserved hydrogen bonding with one or more amino acid residues in the active pocket of EGFR tyrosine kinase (PDB ID: 1m17). The docking score of the derivatives ranged from − 6.7 to − 9.5 kcal mol−1, standard drug Imatinib with − 9.6 kcal mol−1 and standard active ligand 4-anilinoquinazoline with − 7.7 kcal mol−1. The designed compound IV-A1 showed least binding energy (− 9.5 kcal mol−1) against EGFR tyrosine kinase receptor. Further, top scored compound, IV-A1 found to be most significant against MCF-7 cells with IC50 value of 0.0870 µM mL−1, TGI of 0.0958 µM mL−1, GI50 of 0.00499 µM mL−1, LC50 of 1.670 µM mL−1.Item Design, synthesis, and biological evaluation of novel quinoxaline aryl ethers as anticancer agents(Wiley, 2024-03) Murugesan, SankaranarayananWe designed and synthesized thirty novel quinoxaline aryl ethers as anticancer agents, and the structures of final compounds were confirmed with various analytical techniques like Mass, 1H NMR, 13C NMR, FTIR, and elemental analyses. The compounds were tested against three cancer cell lines: colon cancer (HCT-116), breast cancer (MDA-MB-231), prostate cancer (DU-145), and one normal cell line: human embryonic kidney cell line (HEK-293). The obtained results indicate that two compounds, FQ and MQ, with IC50 values < 16 μM, were the most active compounds. Molecular docking studies revealed the binding of FQ and MQ molecules in the active site of the c-Met kinase (PDB ID: 3F66, 1.40 Å). Furthermore, QikProp ADME prediction and the MDS analysis preserved those critical docking data of both compounds, FQ and MQ. Western blotting was used to confirm the impact of the compounds FQ and MQ on the inhibition of the c-Met kinase receptor. The apoptosis assays were performed to investigate the mechanism of cell death for the most active compounds, FQ and MQ. The Annexin V/7-AAD assay indicated apoptosis in MDA-MB-231 cells treated with FQ and MQ, with FQ (21.4%) showing a higher efficacy in killing MDA-MB-231 cells than MQ (14.25%). The Caspase 3/7 7-AAD assay further supported these findings, revealing higher percentages of apoptotic cells for FQ-treated MDA-MB-231 cells (41.8%). The results obtained from the apoptosis assay conclude that FQ exhibits better anticancer activity against MDA-MB-231 cells than MQ.Item Computational screening of some phytochemicals to identify best modulators for ligand binding domain of estrogen receptor alpha(Bentham Science, 2024-06) Murugesan, SankaranarayananThe peculiar aim of this study is to discover and identify the most effective and potential inhibitors against the most influential target ERα receptor by in silico studies of 45 phytochemicals from six diverse ayurvedic medicinal plants. Methods: The molecular docking investigation was carried out by the genetic algorithm program of AutoDock Vina. The molecular dynamic (MD) simulation investigations were conducted using the Desmond tool of Schrödinger molecular modelling. This study identified the top ten highest binding energy phytochemicals that were taken for drug-likeness test and ADMET profile prediction with the help of the web-based server QikpropADME. Results: Molecular docking study revealed that ellagic acid (-9.3 kcal/mol), emodin (-9.1 kcal/mol), rhein (-9.1 kcal/mol), andquercetin (-9.0 kcal/mol) phytochemicals showed similar binding affinity as standard tamoxifen towards the target protein ERα. MD studies showed that all four compounds possess comparatively stable ligand-protein complexes with ERα target compared to the tamoxifen-ERα complex. Among the four compounds, phytochemical rhein formed a more stable complex than standard tamoxifen. ADMET studies for the top ten highest binding energy phytochemicals showed a better safety profile. Conclusion: Additionally, these compounds are being reported for the first time in this study as possible inhibitors of ERα for treating breast cancer, according to the notion of drug repurposing. Hence, these phytochemicals can be further studied and used as a parent core molecule to develop innovative lead molecules for breast cancer therapy.Item In silico studies of phytoconstituents to identify potential inhibitors for erα protein of breast cancer(Bentham Science, 2025-02) Murugesan, SankaranarayananIt is noteworthy that a wide array of plants and nutraceuticals are effectively utilized in the treatment of various cancers, demonstrating potent effects on different cancer targets with fewer side effects. Notably, estrogen alpha has been identified as a crucial factor in breast cancer cell proliferation. Agents that can antagonize its action hold promise as potential drug leads for the treatment of breast cancer.Item Indole Derivatives as Anticancer Agents for Breast Cancer Therapy: A Review(Bentham Science, 2016) Sidhu, Jagpreet SinghBreast cancer (BC) is the second most common cause of cancer-related deaths in women throughout the world. Multiple drugs have been approved by US-FDA for breast related malignancies. Frequent emergence of resistances creates the severe need of newer moieties that are free from such problems. Drugs targeting breast cancer have been observed to be based on the multiple mechanisms of action, and various indole based anticancer agents have also been explored. Moreover, indoles have promising anti-cancer potential; there has been the emphasis on the synthesis of indole derivatives to overcome problems faced by existing therapeutic agents. Taking into consideration the above-mentioned facts we have analyzed in detail the possible role of indole based anticancer agents typically for breast related malignancies. This is the first exhaustive review that jointly covers various synthetic anticancer indole derivatives and related signaling pathways by which these derivatives have shown promising anti-breast cancer potential.Item Physical interaction of estrogen receptor with MnSOD: Implication in mitochondrial O2.− upregulation and mTORC2 potentiation in estrogen-responsive breast cancer cells(Springer, 2016-10) Shrivastava, RichaAugmented reactive oxygen species levels consequential to functional alteration of key mitochondrial attributes contribute to carcinogenesis, either directly via oxidative DNA damage infliction or indirectly via activation of oncogenic signaling cascades. We previously reported activation of a key oncogenic signaling cascade via mammalian target of rapamycin (mTOR) signaling complex-2 (mTORC2) owing to estrogen receptor (ER-α)-dependent augmentation of O2.− within the mitochondria of 17-β-estradiol (E2)-stimulated breast cancer cells. Manganese superoxide dismutase (MnSOD) is the principal mitochondrial attribute governing mitochondrial O2.− homeostasis, raising the possibility that its functional alteration could be instrumental in augmenting mitochondrial O2.− levels in breast cancer cells. Here we show ER-dependent transient inhibition of MnSOD catalytic function in breast cancer cells. Catalytic function of MnSOD is tightly regulated at the post-translational level. Post-translational modifications such as phosphorylation, nitration and acetylation represent key regulatory means governing the catalytic function of MnSOD. Acetylation at lysine-68 (K68) inhibits MnSOD catalytic activity and thus represents an important post-translational regulatory mechanism in human cells. Using reciprocal immunoprecipitation and proximity ligation assay, we demonstrate the occurrence of direct physical interaction between ER-α and MnSOD in human breast cancer cells, which in turn was associated with potentiated acetylation of MnSOD at K68. In addition, we also observed diminished interaction of MnSOD with sirtuin-3, the key mitochondrial deacetylase that deacetylates MnSOD at critical K68 and thereby activates it for scavenging O2.−. Consequently, compromised deacetylation of MnSOD at K68 leading to its inhibition and a resultant buildup of O2.− within the mitochondria culminated in the activation of mTORC2. In agreement with this, human breast cancer tissue specimen exhibited a positive correlation between acetyl-MnSODK68 levels and phospho-Ser2481 mTOR levels. In addition to exposing the crosstalk of ER-α with MnSOD post-translational regulatory mechanisms, these data also unravel a regulatory role of ER/MnSOD interaction as an important control switch for redox regulation of ER-α-responsive oncogenic signaling cascades. Furthermore, our study provides a mechanistic link for ER-α-dependent O2.− potentiation and resultant mTORC2 activation in breast cancer cellsItem Macrophages are recruited to hypoxic tumor areas and acquire a Pro-Angiogenic M2-Polarized phenotype via hypoxic cancer cell derived cytokines Oncostatin M and Eotaxin(Impact Journals, LLC, 2014-06) Shrivastava, RichaTAMs, a unique and distinct M2-skewed myeloid population of tumor stroma, exhibiting pro-tumor functions is fast emerging as a potential target for anti-cancer immunotherapy. Macrophage-recruitment and M2-polarization represent key TAMs-related phenomenon that are amenable to therapeutic intervention. However successful translation of these approaches into effective therapeutic regimen requires better characterization of tumor-microenvironment derived signals that regulate macrophage recruitment and their polarization. Owing to hypoxic milieu being a persistent feature of tumor-microenvironment and a major contributor to malignancy and treatment resistance, the current study was planned with an aim to decipher tumor cell responses to hypoxia vis-a-vis macrophage homing and phenotype switching. Here, we show that hypoxia-primed cancer cells chemoattract and polarize macrophages to pro-angiogenic M2-polarized subtype via Eotaxin and Oncostatin M. Concordantly, hypoxic regions of human breast-cancer specimen exhibited elevated Eotaxin and Oncostatin M levels with concurrently elevated M2-macrophage content. Blockade of Eotaxin/Oncostatin M not only prevented hypoxic breast-cancer cells from recruiting and polarizing macrophages towards an M2-polarized phenotype and retarded tumor progression in 4T1/BALB/c-syngenic-mice-model of breast-cancer but also enhanced the efficacy of anti-angiogenic Bevacizumab. The findings established these two cytokines as novel targets for devising effective anticancer therapy particularly for tumors that are refractory or develop resistance to anti-angiogenic therapeutics.Item Disulfiram potentiates docetaxel cytotoxicity in breast cancer cells through enhanced ROS and autophagy(Springer, 2020-07) Chowdhury, Rajdeep; Roy, AniruddhaRecent studies have demonstrated that autophagy plays a critical role in reducing the drug sensitivity of docetaxel (DTX) therapy. Disulfiram (DSF) has exhibited potent autophagy inducing activity in multiple studies. We hypothesized that DSF co-treatment could sensitize breast cancer cells to DTX therapy via autophagy modulation.Item Belinostat loaded lipid–polymer hybrid nanoparticulate delivery system for breast cancer: improved pharmacokinetics and biodistribution in a tumor model(RSC, 2023-10) Chitkara, Deepak; Mittal, AnupamaDespite various treatment modalities for breast cancer, it still persists as one of the most diagnosed types of cancer in females. The recent investigations in the epigenetics of breast cancer reveal several aberrations in the expression levels of various HDAC enzymes. Henceforth, the present work entails the formulation and characterization of a lipid polymer-based hybrid nanoparticulate (LPN) system for delivery of an epigenetic modulator drug, Belinostat, for its clinical application in breast cancer. The size of Belinostat nanoparticles prepared using a modified hot homogenization method was found to be 166.6 ± 19.95 nm with an encapsulation efficiency of 94.5 ± 5.1%. In vitro characterization for cytotoxicity, cellular uptake, and protein expression in two different breast cancer cells, 4T1 and MCF 7, revealed the superiority of the formulation in comparison with the free drug in MCF 7 cells. Subsequently, the behaviour of the formulation in in vivo settings of healthy and breast cancer xenograft bearing animals was analyzed using pharmacokinetic and biodistribution studies. The results revealed that the formulation demonstrated multi-fold improvement in the pharmacokinetic parameters in tumor bearing animals when compared with the free drug while no difference in pharmacokinetic behaviour was observed in healthy animals indicating the altered biodistribution and specificity of the formulation in breast tumor. This was confirmed by the biodistribution studies exhibiting 20-fold improved uptake and retention of the nanoparticulate formulation in tumor tissues of the animal model at the end of 4 h. Thus, the developed LPN system holds potential to act as a novel drug delivery system for Belinostat with several advantages over the free drug.