Browsing by Author "Saurabh Sharma"

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Anti-metastatic cancer potential of 4H-chromene derivatives targeting JNK in Scribble knockdown induced epithelial cancer model: In vivo and in silico studies
(Academic Press Inc., 2025) Vaishali Raghuvanshi; Jyotsna Singh; Saurabh Sharma; Ray Jay Butcher; Saripella Srikrishna; Diksha Katiyar
Building on our previous work on the synthesis of a series of 4H-chromene derivatives, we report herein for the first time the in vivo and in silico studies of ten chromene derivatives 5a-j as potential anti-metastatic cancer agents targeting through c-Jun N-terminal kinase (JNK). Compounds 5a-j were resynthesized using the protocol previously reported by our research group. Out of these, 5c, 5f-h and 5j showed good anti-metastatic cancer activity in Drosophila in vivo model, with 5f being the most active. It exhibited 27% rescue in metastatic cancer induced pupal lethality, whereas the standard drug sorafenib showed no rescue. Furthermore, 5f has significantly downregulated JNK and the metastasis promoting marker enzyme, matrix metalloproteinase-1 (MMP1) expression in Scribble (Scrib) knockdown induced Drosophila cancer tissues. In silico studies of all the compounds, 5a-j, demonstrated strong binding affinity with Drosophila JNK protein (PDB ID: 5AWM). Additionally, comparison of the docking positions of 5f in the 5AWM and human JNKs (PDB IDs: 1UKH and 3E7O) binding sites revealed a high degree of homology between them with respect to the similar set of amino acids interacting with the ligand. Compounds 5a-j also exhibited favourable pharmacokinetic properties with drug-like characteristics, as predicted by SwissADME analysis. The crystal structure of 5f was determined for the first time using single-crystal X-ray diffraction (SC-XRD) analysis. It crystallizes in a monoclinic crystal system with the space group P21/c, providing valuable insights into its structural features and molecular arrangement. The present findings strongly suggest that the chromene derivatives, represented by compound 5f, hold promise as potential anticancer agents targeting the metastatic stage in various epithelial cell-derived cancers. © 2025 Elsevier Inc.
Clinical Abacavir Hypersensitivity Reaction among Children in India
(Springer India, 2016) Jaya Chakravarty; Saurabh Sharma; Anuradha Johri; Ankita Chourasia; Shyam Sundar
Abacavir is currently recommended as a part of first line regimen by National AIDS Control Organization. The objective of this study was to observe the incidence of clinically diagnosed abacavir Hypersensitivity reaction (HSR) among children on abacavir based therapy in the National program. In this observational study, all children started on abacavir were included and HSR reaction was diagnosed clinically as per National guidelines. HLA- B*5701 testing was done in children diagnosed with clinical abacavir HSR. Among 101 children started on abacavir during the study period, 8 [7.9 % (95 % CI 3.5-15.0 %)] children developed clinically diagnosed abacavir HSR. All children with concomitant illness (4/8) were HLA-B*5701 negative. Only 2 (25 %, 2/8) carried HLA-B*5701 allele. Fever with abdominal symptoms as compared to respiratory symptoms were more common in HLA-B*5701 positive cases. Overdiagnosis of clinically diagnosed abacavir HSR is common and could be decreased by treating concomitant illness before starting abacavir. © 2016, Dr. K C Chaudhuri Foundation.
Modeling of rupture using strong motion generation area: a case study of Hualien earthquake (M w 6.1) occurred on April 18, 2019
(Springer Science and Business Media Deutschland GmbH, 2023) Saurabh Sharma; Anand Joshi; Sandeep; Che-Min Lin; Chun-Hsiang Kuo; Kuo-Liang Wen; Sandeep Singh; Mukat Lal Sharma; Mohit Pandey; Jyoti Singh
The strong Hualien earthquake (Mw 6.1) occurred along the suture zone of the Eurasian Plate and the Philippine Sea Plate, which struck the Hualien city in eastern Taiwan on April 18, 2019. The focal mechanism of this earthquake shows that it is caused by a rupture within a thrust. In the present study, the rupture plane responsible for this earthquake has been modeled using the modified semi-empirical technique (MSET). The whole rupture plane is assumed to be composed of strong motion generation areas (SMGAs) along which the slip occurs with large velocities. The spatiotemporal distribution of aftershocks of this earthquake within identified rupture plane suggests that there are two SMGAs within the rupture plane. The source displacement spectra (SDS) obtained from the observed records have been used to compute the source parameters of these two SMGAs. The MSET efficiently simulates strong ground motion (SGM) at the rock site. The shallow subsurface shear wave velocity profile at various stations has been used as an input to SHAKE91 algorithm for converting records at the surface to that at the rock site. The simulated records are compared with the observed records based on root-mean-square error (RMSE) in peak ground acceleration (PGA) of horizontal components. Various parameters of the rupture plane have been selected using an iterative forward modeling scheme. The accelerograms have been simulated for all the stations that lie within an epicentral distance ranging from 5 to 100 km using the final rupture plane parameters. The comparison of observed and synthetic records validates the effectiveness of the simulation technique and suggests that the Hualien earthquake consists of two SMGAs responsible for high-frequency SGM. © 2022, The Author(s) under exclusive licence to Institute of Geophysics, Polish Academy of Sciences & Polish Academy of Sciences.
Prevalence of HLA-B*57:01 allele in HIV-positive and HIV-negative population of eastern India: An epidemiological study
(Elsevier B.V., 2022) Abhilasha Gautam; Jaya Chakravarty; Ankita Chourasia; Saurabh Sharma; Tanmoy Sarkar; Parimal Das
Introduction: The nucleoside analogue reverse-transcriptase inhibitor Abacavir has potent antiviral activity against HIV; however, 5–8% patients develop hypersensitivity reactions within six weeks of treatment. The presence of the HLA-B*57:01 allele is strongly associated with the risk of Abacavir-associated hypersensitivity reaction (ABC-HSR). Prevalence of HLA-B*57:01 allele varies in different populations. This observational study was performed to determine the prevalence of HLA-B*57:01 allele in the population of Eastern India which included both HIV-positive and HIV-negative subjects. Methods: We screened 406 subjects attending the ART (antiretroviral treatment) centre and linked ICTC (Integrated counselling and testing centre), however 6 samples did not have adequate DNA. HLA-B*57:01 typing was done using direct sequence specific primer PCR (SSP-PCR). All PCR positive samples were sequenced using Sanger's method. Results: The prevalence of HLA-B*57:01 genotype in our cohort was 12.25% (49/400). Prevalence among men was 13.3% (33/248) and female was 10.5% (16/152). The prevalence was similar in HIV-positive subjects (13.5%) and in HIV-negative subjects (11%). Conclusions: Prevalence of HLA-B*57:01 in our eastern Indian population was high. Therefore, screening for HLA-B*57:01 before ABC administration would be useful to prevent ABC-HSR. © 2022
Research on the interstellar medium and star formation in the Galaxy: An Indian perspective
(Springer, 2025) Bhaswati Mookerjea; Gopinathan Maheswar; Kinsuk Acharyya; Tapas Baug; Prasun Datta; Jessy Jose; Devandra K. Ojha; Jagadheep D. Pandian; Nirupam Roy; Manash R. Samal; Saurabh Sharma; Archana Soam; Sarita Vig; Ankan Das; Lokesh Kumar Dewangan; Somnath Dutta; C. Eswariah; Liton Majumdar; Kshitiz Kumar Mallick; Soumen K. Mondal; Joe Philip Ninan; Neelam Panwar; Amit Pathak; Shantanu Rastogi; Dipen Sahu; Anandmayee Tej; Vadamattom S. Veena
Although the star-formation process has been studied for decades, many important aspects of the physics involved remain unsolved. Recent advancements in instrumentation in the infrared, far-infrared, and sub-millimeter-wavelength regimes have contributed to a significantly improved understanding of processes in the interstellar medium (ISM) leading to star formation. The future of research on the ISM and star formation looks exciting with instruments like the JWST, ALMA, etc., already contributing to the topic by gathering high-resolution high-sensitivity data and with several larger ground- and space-bound facilities either being planned or constructed. India has a sizable number of astronomers engaged in research on topics related to the ISM and star formation. In this white paper invited by the Astronomical Society of India to prepare a vision document for Indian astronomy, we review the Indian contributions to the global understanding of the star-formation process and suggest areas that require focused efforts both in creating observing facilities and in the theoretical front in India, to improve the impact of our research in the coming decades. © Indian Academy of Sciences 2024.
Synthesis, In Vitro and In Vivo Antifungal Activities of Novel Coumarin–Tryptophan Conjugates
(Pleiades Publishing, 2025) Neha Tiwari; Ankita Kumari; Saurabh Sharma; Vaishali Raghuvanshi; Gunjan Uttam; Vineeta K. Singh; Karuna Singh; Diksha Katiyar
Abstract: Objective: Persistent fungal infections, especially those caused by Candida spp., pose a serious health risk to humans. Treatment of these infections is highly challenging due to the spread of resistance to first-line antifungal drugs. Therefore, the identification and development of novel antifungal agents are in great demand. In this study, a series of coumarin–tryptophan conjugates were synthesized and their antifungal activities evaluated. Methods:In vitro antifungal activities of compounds (IVa–IVe) were determined by the minimum inhibitory concentration (MIC) method. The in vivo activity of the most active compound, (IVe), was assessed using a murine model of dermal candidiasis. Docking studies were performed using the AutoDock 4.0 software package. Results and Discussion: Several compounds exhibited broad-spectrum activity against the tested strains, with favorable MIC values in the range of 6.25–25 µg/mL. Compound (IVe) showed significant antifungal activity with an MIC of 6.25 µg/mL against A. flavus and C. albicans. In the murine dermal candidiasis model, (IVe) reduced the fungal burden in nearly all vital organs of the experimental animals and demonstrated therapeutic healing effects on ulcers induced by C. albicans infection. Molecular docking results indicated that these compounds have potential as antifungal agents. Evaluation of drug-like properties of compounds (IVa–IVe) using the SwissADME web tool revealed that these molecules possess favorable druggability profiles. Conclusions: Compound (IVe), having shown excellent antifungal activity, can be considered a promising antifungal agent for further investigation. © Pleiades Publishing, Ltd. 2025.