Browsing by Author "Kaur, Gagandeep"

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    Design and synethesis of APE1 inhibitors as putative anticancer agents
    (Central University of Punjab, 2014) Kaur, Gagandeep; Kumar, Raj
    Success in chemotherapy has not been attained completely yet and has remained a worried issue from years. Various reasons drive this failure, but the much talked about is failure due to emergence of resistance to chemotherapeutic drugs due to various factors. One of the major reasons here we have targeted is the resistance developed against DNA damaging chemotherapy due to over activation of APE1 enzyme evolved in BER pathway, which is the major repair pathway responsible for 95% of the DNA repair. Design and synthesis of APE1 inhibitors using rational approach fulfilling the pharmacophoric requirements has been carried out in this research work. Molecular modelling studies were performed to confirm that designed compounds fit well into the repair active cavity. 14 compounds have been designed and synthesized having pyrazolo-quinazolines core structure. The anticancer potential of the 8 representative compounds was evaluated against rat C-6 glial cell line at different concentrations. All synthesized compounds showed good anticancer activity against rat C-6 glial cell lines. The inhibitory potential of the compounds obtained from the MTT assay results helped us to formulate the SAR studies. Further ROS measurement was also carried out using DCFDA assay. Compounds showing good MTT results were also found to be potential antioxidants which conclude their mechanism of anticancer activity through APE1 inhibition. The active compounds may be taken further for lead optimisation and mechanistic interventions for their in vitro binding studies on APE1 in future.
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    DNA Origami-Templated Bimetallic Core-Shell Nanostructures for Enhanced Oxygen Evolution Reaction
    (American Chemical Society, 2022-04-15T00:00:00) Kaur, Gagandeep; Biswas, Rathindranath; Haldar, Krishna Kanta; Sen, Tapasi
    Hydrogen generation through electrocatalytic water splitting offers promising technology for sustainable and clean energy production as an alternative to conventional energy sources. The development of highly active electrocatalysts is of immense interest for improving the efficiency of gas evolution, which is strongly hindered due to the sluggish kinetics of oxygen evolution reaction (OER). Herein, we present the design of Ag-coated Au nanostar (core-shell-type Au@Ag nanostar) monomer structures assembled on rectangular DNA origami and study their electrocatalytic activities through OER, which remains unexplored. Our designed DNA origami-templated bimetallic nanostar catalyst showed excellent OER activity and high stability without using any external binder and exhibited a current density of 10 mA cm-2at a low overpotential of 266 mV, which was smaller than those of ss-DNA-functionalized Au@Ag nanostars and DNA origami-templated pure Au nanostars. Our results reveal that DNA origami-assembled core-shell Au@Ag nanostars show better electrocatalytic performance as compared to pure-core Au nanostars immobilized on DNA origami, owing to the presence of a highly conductive Ag layer. Such controlled assembly of bimetallic nanostructures on a DNA origami template can provide additional electrochemical surface area and a higher density of active sites resulting in enhanced electrocatalysis. � 2022 American Chemical Society. All rights reserved.
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    DNA Repair and Redox Activities and Inhibitors of Apurinic/ Apyrimidinic Endonuclease 1/Redox Effector Factor 1 (APE1/Ref-1): A Comparative Analysis and Their Scope and Limitations toward Anticancer Drug Development
    (ACS Publications, 2014) Kaur, Gagandeep; Cholia, Ravi P.; Mantha, Anil K.; Kumar, Raj
    The apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional enzyme involved in DNA repair and activation of transcription factors through its redox function. The evolutionarily conserved C- and N-termini are involved in these functions independently. It is also reported that the activity of APE1/Ref-1 abruptly increases several-fold in various human cancers. The control over the outcomes of these two functions is emerging as a new strategy to combine enhanced DNA damage and chemotherapy in order to tackle the major hurdle of increased cancer cell growth and proliferation. Studies have targeted these two domains individually for the design and development of inhibitors for APE1/Ref-1. Here, we have made, for the first time, an attempt at a comparative analysis of APE1/Ref-1 inhibitors that target both DNA repair and redox activities simultaneously. We further discuss their scope and limitations with respect to the development of potential anticancer agents.
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    Interfacial design of gold/silver core-shell nanostars for plasmon-enhanced photocatalytic coupling of 4-aminothiophenol
    (Royal Society of Chemistry, 2021-10-02T00:00:00) Kaur, Gagandeep; Tanwar, Swati; Kaur, Vishaldeep; Biswas, Rathindranath; Saini, Sangeeta; Haldar, Krishna Kanta; Sen, Tapasi
    Chemical reactions under mild conditions mediated by localized surface plasmon resonance (LSPR) of metals have emerged as a functional research field. In the present study, we report an interfacial designing procedure for the fabrication of a class of bimetallic hybrid nanomaterials as a profoundly active photocatalyst for the conversion of para-aminothiophenol (PATP) into 4,4?-dimercaptoazobenzene. For this purpose, core-shell nanostars composed of gold (core) and silver (shell) (Au/Ag NSs) were utilized as both surface-enhanced Raman scattering substrate and plasmon driven catalyst under 532 nm laser excitation. Au/Ag NSs with sharp tips display excellent surface-enhanced Raman scattering (SERS) efficiency of PATP. Employing the SERS study, it has been found that PATP rapidly converts into its dimerized product DMAB within few seconds by surface photochemical reaction in the Au-Ag heterojunction of core-shell nanostars. Au/Ag NSs with multiple sharp tips exhibit intense LSPR and highly strong electric fields are created at the tips, which enables the generation of hot electrons responsible for the rapid conversion reaction. Such well-designed interfacial bimetallic nanostars could have potential applications in surface enhanced spectroscopy, biosensing, and photoinduced surface catalysis. This journal is � The Royal Society of Chemistry.
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    Interfacial Engineering of CuCo2S4/g-C3N4Hybrid Nanorods for Efficient Oxygen Evolution Reaction
    (American Chemical Society, 2021-07-29T00:00:00) Biswas, Rathindranath; Thakur, Pooja; Kaur, Gagandeep; Som, Shubham; Saha, Monochura; Jhajhria, Vandna; Singh, Harjinder; Ahmed, Imtiaz; Banerjee, Biplab; Chopra, Deepak; Sen, Tapasi; Haldar, Krishna Kanta
    Altering the morphology of electrochemically active nanostructured materials could fundamentally influence their subsequent catalytic as well as oxygen evolution reaction (OER) performance. Enhanced OER activity for mixed-metal spinel-type sulfide (CuCo2S4) nanorods is generally done by blending the material that has high conductive supports together with those having a high surface volume ratio, for example, graphitic carbon nitrides (g-C3N4). Here, we report a noble-metal-free CuCo2S4 nanorod-based electrocatalyst appropriate for basic OER and neutral media, through a simple one-step thermal decomposition approach from its molecular precursors pyrrolidine dithiocarbamate-copper(II), Cu[PDTC]2, and pyrrolidine dithiocarbamate-cobalt(II), Co[PDTC]2 complexes. Transmission electron microscopy (TEM) images as well as X-ray diffraction (XRD) patterns suggest that as-synthesized CuCo2S4 nanorods are highly crystalline in nature and are connected on the g-C3N4 support. Attenuated total reflectance-Fourier-transform infrared (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy studies affirm the successful formation of bonds that bridge (Co-N/S-C) at the interface of CuCo2S4 nanorods and g-C3N4. The kinetics of the reaction are expedited, as these bridging bonds function as an electron transport chain, empowering OER electrocatalytically under a low overpotential (242 mV) of a current density at 10 mA cm-2 under basic conditions, resulting in very high durability. Moreover, CuCo2S4/g-C3N4 composite nanorods exhibit a high catalytic activity of OER under a neutral medium at an overpotential of 406 mV and a current density of 10 mA cm-2. � 2021 American Chemical Society.
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    Synthesis and xanthine oxidase inhibitory activity of 5,6 dihydropyrazolo/pyrazolo[1,5-c]quinazoline derivatives
    (Elsevier, 2014) Kumar, Deependra; Kaur, Gagandeep; Negi, Arvind; Kumar, Sanjeev; Singh, Sandeep; Kumar, Raj
    Some 5,6-dihydropyrazolo/pyrazolo[1,5-c]quinazoline derivatives were rationally designed, synthesized and evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Some notions about structure activity relationships are presented. The compounds 6g, 6h and 6e were found to be significantly active against XO. The compound 6g emerged as the most potent XO inhibitor as compared to allopurinol and free radical scavenger. The molecular docking of 6g into the XO active site highlighted its mode of binding and important interactions such as hydrogen bonding, π–π stacking with amino acid residues like Ser876, Thr1010, Phen914, Phe1009 and Phe649 and its close proximity to dioxothiomolybdenum (MOS).
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    Therapeutic targeting of angiopoietins in tumor angiogenesis and cancer development
    (Elsevier B.V., 2023-10-21T00:00:00) Thapa, Komal; Khan, Heena; Kaur, Gagandeep; Kumar, Puneet; Singh, Thakur Gurjeet
    The formation and progression of tumors in humans are linked to the abnormal development of new blood vessels known as neo-angiogenesis. Angiogenesis is a broad word that encompasses endothelial cell migration, proliferation, tube formation, and intussusception, as well as peri-EC recruitment and extracellular matrix formation. Tumor angiogenesis is regulated by angiogenic factors, out of which some of the most potent angiogenic factors such as vascular endothelial growth factor and Angiopoietins (ANGs) in the body are produced by macrophages and other immune cells within the tumor microenvironment. ANGs have a distinct function in tumor angiogenesis and behavior. ANG1, ANG 2, ANG 3, and ANG 4 are the family members of ANG out of which ANG2 has been extensively investigated owing to its unique role in modifying angiogenesis and its tight association with tumor progression, growth, and invasion/metastasis, which makes it an excellent candidate for therapeutic intervention in human malignancies. ANG modulators have demonstrated encouraging outcomes in the treatment of tumor development, either alone or in conjunction with VEGF inhibitors. Future development of more ANG modulators targeting other ANGs is needed. The implication of ANG1, ANG3, and ANG4 as probable therapeutic targets for anti-angiogenesis treatment in tumor development should be also evaluated. The article has described the role of ANG in tumor angiogenesis as well as tumor growth and the treatment strategies modulating ANGs in tumor angiogenesis as demonstrated in clinical studies. The pharmacological modulation of ANGs and ANG-regulated pathways that are responsible for tumor angiogenesis and cancer development should be evaluated for the development of future molecular therapies. � 2023 Elsevier Inc.