http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/1931 Tue, 21 Apr 2026 15:58:03 GMT 2026-04-21T15:58:03Z http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/20032 S-nitrosylation of EZH2 alters PRC2 assembly, methyltransferase activity, and EZH2 stability to maintain endothelial homeostasis Sundriyal, Sandeep; Chowdhury, Shibasish; Majumder, Syamantak Nitric oxide (NO), a versatile bio-active molecule modulates cellular functions through diverse mechanisms including S-nitrosylation of proteins. Herein, we report S-nitrosylation of selected cysteine residues of EZH2 in endothelial cells, which interplays with its stability and functions. We detect a significant reduction in H3K27me3 upon S-nitrosylation of EZH2 as contributed by the early dissociation of SUZ12 from the PRC2. Moreover, S-nitrosylation of EZH2 causes its cytosolic translocation, ubiquitination, and degradation. Further analysis reveal S-nitrosylation of cysteine 329 induces EZH2 instability, whereas S-nitrosylation of cysteine 700 abrogates its catalytic activity. We further show that S-nitrosylation-dependent regulation of EZH2 maintains endothelial homeostasis in both physiological and pathological settings. Molecular dynamics simulation reveals the inability of SUZ12 to efficiently bind to the SAL domain of EZH2 upon S-nitrosylation. Taken together, our study reports S-nitrosylation-dependent regulation of EZH2 and its associated PRC2 complex, thereby influencing the epigenetics of endothelial homeostasis. Tue, 01 Apr 2025 00:00:00 GMT http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/20032 2025-04-01T00:00:00Z http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/20031 Harnessing antimalarial chemical space: the way forward Sundriyal, Sandeep Malaria remains a major health challenge, with increasing resistance to frontline chemotherapy. Recent cheminformatics studies have revealed that potent antiplasmodials occupy a distinct antimalarial chemical space (AMCS), defined by specific property cutoffs. Wed, 01 Oct 2025 00:00:00 GMT http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/20031 2025-10-01T00:00:00Z http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/20030 Current status of Liraglutide delivery systems for the management of type 2 diabetes mellitus Jindal, Anil B. Diabetes is a metabolic disorder of increasing global concern. Characterized by constantly elevated levels of glucose, severe β-cell dysfunction, and insulin resistance, it is the cause of a major burden on patients if not managed with therapeutic and lifestyle changes. The human body is slowly developing tolerance to many marketed antidiabetic drugs and the quest for the discovery of newer molecules continues. Liraglutide is a prominent GLP-1 receptor agonist which is administered daily via subcutaneous injection. In addition to lowering HbA1c levels, it is also known for promoting weight loss and improving cardiovascular outcomes. A variety of novel formulation strategies have been explored to improve its bioavailability and patient compliance. To address these limitations, various advanced drug delivery systems have been investigated, including polymeric nanoparticles, lipid-based nanocarriers, biodegradable microparticles, hydrogels, and dissolvable microneedles. These systems aim to prolong drug release, enhance mucosal penetration, increase stability, and reduce dosing frequency. While many of these platforms show promise in preclinical and early clinical studies, critical translational barriers remain. These include challenges in large-scale manufacturing, ensuring formulation sterility, achieving regulatory approval, and maintaining stability during storage and distribution. Mon, 01 Sep 2025 00:00:00 GMT http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/20030 2025-09-01T00:00:00Z http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/20029 Exploration of quinoxaline triazoles as antimycobacterial agents: design, synthesis and biological evaluation Murugesan, Sankaranarayanan In this work, novel 2-substituted-3-((1-substituted-1H-1,2,3-triazol-4-yl) methoxy) quinoxaline analogues were designed, synthesized, and various analytical techniques, viz., 1H NMR, 13C NMR, and Mass spectrometry, were deployed in the structure confirmation of the final compounds. Synthesized derivatives were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis (Mtb) H37Rv. Target molecules mainly consist of methyl substituent in the second position of quinoxaline moiety (QM series) or phenyl substituent in the second position (QP series). Among the forty-two compounds synthesized and evaluated for anti-mycobacterial activity, the MIC values ranged between 5.58 μg/mL to >100 μg/mL. Among QM series compounds, QM7, with MIC 5.58 μg /mL, was the most active compound. Among the QP series derivatives, the intermediate QP-Acy with MIC 23.39 μg /mL was the most promising. Most of the analogues tested in the QP series are less potent than the QM series. All the synthesized molecules showed good drug-likeness when evaluated using the SWISS ADME tool. QM7 was evaluated for docking studies using the crystal structure of enoyl-acyl carrier (INH-A) enzyme PDB: 4TZK, and it showed significant docking scores and interactions. MD simulations were carried out to assess the stability of the protein QM7 complex. Single crystals were grown for QM1, QM6, and QPb from these forty-two compounds, and their structures were solved using OLEX. The corresponding CCDC numbers for these compounds are 2,388,310, 2,388,309, and 2,388,291, respectively. Sun, 01 Jun 2025 00:00:00 GMT http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/20029 2025-06-01T00:00:00Z