Browsing by Author "Sindhu, Jayant"

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Electro-organic synthesis of C-5 sulfenylated amino uracils: Optimization and exploring topoisomerase-I based anti-cancer profile
(Academic Press Inc., 2023-06-10T00:00:00) Rani, Payal; Chahal, Sandhya; Kumar, Roshan; Mayank; Kumar, Parvin; Negi, Arvind; Singh, Rajvir; Kumar, Sudhir; Kataria, Ramesh; Joshi, Gaurav; Sindhu, Jayant
Cancer is spreading worldwide and is one of the leading causes of death. The use of existing chemotherapeutic agents is frequently limited due to side effects. As a result, it is critical to investigate new agents for cancer treatment. In this context, we developed an electrochemical method for the synthesis of a series of thiol-linked pyrimidine derivatives (3a-3p) and explored their anti-cancer potential. The biological profile of the synthesized compounds was evaluated against breast (MDAMB-231 and MCF-7) and colorectal (HCT-116) cancer cell lines. 3b and 3d emerged to be the most potent agents, with IC50 values ranging between 0.98 to 2.45 �M. Target delineation studies followed by secondary anticancer parameters were evaluated for most potent compounds, 3b and 3d. The analysis revealed compounds possess DNA intercalation potential and selective inhibition towards human topoisomerase (hTopo1). The analysis was further corroborated by DNA binding studies and in silico-based molecular modeling studies that validated the intercalating binding mode between the compounds and the DNA. � 2023 Elsevier Inc.
Precisely designed oxazolonaphthoimidazo[1,2-a]pyridine-based sensor for the detection of Fe3+ and DCP with cell imaging application
(Elsevier B.V., 2023-05-17T00:00:00) Kathuria, Vishal; Kiran; Rani, Payal; Mayank; Joshi, Gaurav; Kumar, Roshan; Sindhu, Jayant; Kumar, Parvin; Negi, Arvind; Kumar, Sudhir
Two new turn-off fluorescent sensors (V3 and V4) presented in the article revealed the potential application for the precise detection of Fe3+ and diethylchlorophosphate (DCP). These sensors include oxazolonaphthoimidazo[1,2-a]pyridine scaffold integrated with anthracene and pyrene-based framework. This design has facilitated the twisted intramolecular charge transfer (TICT) and planarised intramolecular charge transfer (PLICT) mechanisms, which were confirmed using computational and photophysical studies. The V3 and V4 fluorescent probes were particularly sensitive and highly selective for detecting Fe3+ and DCP analytes. For Fe3+, V3 and V4 undergo turn-off mechanism with the detection limit of 14.1 and 4.5 nM, respectively. Intracellular detection of Fe3+ via confocal live cell imaging was also demonstrated, showing its application under intracellular conditions. Our experimental data revealed the promises of V3 and V4 for instantaneous, accurate and on-spot monitoring of Fe3+ and DCP, even in the presence of other interfering analytes. � 2023 Elsevier B.V.
Precisely designed oxazolonaphthoimidazo[1,2-a]pyridine-based sensor for the detection of Fe3+ and DCP with cell imaging application
(Elsevier B.V., 2023-05-17T00:00:00) Kathuria, Vishal; Kiran; Rani, Payal; Mayank; Joshi, Gaurav; Kumar, Roshan; Sindhu, Jayant; Kumar, Parvin; Negi, Arvind; Kumar, Sudhir
Two new turn-off fluorescent sensors (V3 and V4) presented in the article revealed the potential application for the precise detection of Fe3+ and diethylchlorophosphate (DCP). These sensors include oxazolonaphthoimidazo[1,2-a]pyridine scaffold integrated with anthracene and pyrene-based framework. This design has facilitated the twisted intramolecular charge transfer (TICT) and planarised intramolecular charge transfer (PLICT) mechanisms, which were confirmed using computational and photophysical studies. The V3 and V4 fluorescent probes were particularly sensitive and highly selective for detecting Fe3+ and DCP analytes. For Fe3+, V3 and V4 undergo turn-off mechanism with the detection limit of 14.1 and 4.5 nM, respectively. Intracellular detection of Fe3+ via confocal live cell imaging was also demonstrated, showing its application under intracellular conditions. Our experimental data revealed the promises of V3 and V4 for instantaneous, accurate and on-spot monitoring of Fe3+ and DCP, even in the presence of other interfering analytes. � 2023 Elsevier B.V.
Recent efforts for drug identification from phytochemicals against SARS-CoV-2: Exploration of the chemical space to identify druggable leads
(Elsevier Ltd, 2021-04-03T00:00:00) Joshi, Gaurav; Sindhu, Jayant; Thakur, Shikha; Rana, Abhilash; Sharma, Geetika; Mayank; Poduri, Ramarao
Nature, which remains a central drug discovery pool, is always looked upon to find a putative druggable lead. The natural products and phytochemical derived from plants are essential during a global health crisis. This class represents one of the most practical and promising approaches to decrease pandemic's intensity owing to their therapeutic potential. The present manuscript is therefore kept forth to give the researchers updated information on undergoing research in allied areas of natural product-based drug discovery, particularly for Covid-19 disease. The study briefly shreds evidence from in vitro and in silico researches done so far to find a lead molecule against Covid-19. Following this, we exhaustively explored the concept of chemical space and molecular similarity parameters for the drug discovery about the lead(s) generated from in silico-based studies. The comparison was drawn using FDA-approved anti-infective agents during 2015�2020 using key descriptors to evaluate druglike properties. The outcomes of results were further corroborated using Molecular Dynamics studies which suggested the outcomes in alignment with chemical space ranking. In a nutshell, current research work aims to provide a holistic strategic approach to drug design, keeping in view the identified phytochemicals against Covid-19. � 2021 Elsevier Ltd
Structural Diversity of D-Alanine: D-Alanine Ligase and Its Exploration in Development of Antibacterial Agents Against the Multi-Variant Bacterial Infections
(John Wiley and Sons Inc, 2022-04-07T00:00:00) Mayank; Sidhu, Jagpreet Singh; Joshi, Gaurav; Sindhu, Jayant; Kaur, Navneet; Singh, Narinder
D-alanine: D-alanine ligase (Rv2981c or Ddl) (EC 6.3.2.4) is a bacterial protein that performs critical functions for the proper growth and development of bacterial cells. Understanding the activity profile of Ddl within the various strains of the bacteria seems vital in broad-spectrum antimicrobial drug discovery. Therefore, to understand this heterologous nature, we focused on understanding the functional impact of the structural differences in the Ddl protein from Legionella pneumophila and E. coli bacteria. The structural features and dynamic behavior of Ddl, the interaction pattern, and the docking score of the Ddl-ATP/ADP are also found significantly different from each other. In-depth analysis viz molecular dynamics simulation and residue interaction network (RIN) studies provided us the detailed insight into the differences in the Ddl proteins from both the bacteria. In conclusion, understanding the inter-specific differences in the antibiotic targets Ddl in the case of diverse bacterial strains is vital for rationalizing the treatment of these infectious diseases. Therefore, the current work attempts to foresee the development of more efficacious antibacterial agents devoid of emerging resistance to bacterium strains. � 2022 Wiley-VCH GmbH.