Exploring imidazo[1,2-a]pyridine hybrids in cancer therapy: ADMET profiling, molecular docking, MD simulations and DFT calculations Drashti Shah, Afzal Nagani, Moksh Shah, Ashish Patel Scientific Reports, 2026 Cyclin dependent kinase 2 (CDK2) is a critical regulator of cell cycle progression and an important therapeutic target in cancer treatment. In this study, imidazo[1,2-a]pyridine-quinazoline hybrids were computationally explored as potential CDK2 inhibitors using an integrated in silico framework. Virtual screening enabled the prioritization of compounds exhibiting favourable interactions with the CDK2 active site particularly through hinge region residues. Among the screened library, two compounds AD20 and AD28 emerged as top ranked based on a consensus assessment of binding affinity and predicted pharmacokinetic suitability. These compounds demonstrated stable binding behaviour, favourable drug likeness, and electronic features supportive of molecular stability and reactivity. Importantly, the findings represent computational prioritization rather than experimental validation. Overall, this study highlights imidazo[1,2-a]pyridine hybrids as promising scaffolds for further optimization and provides a rational basis for future experimental evaluation toward CDK2 targeted anticancer drug development.
Benzothiazole-Based Anti-Alzheimer's Agents: A Comprehensive Review of Developments from 2015 to 2025 Moksh Shah, Sudhanshu Sinha, Meetali Bhasme, Mange Ram Yadav, Afzal Nagani Chemical Record, 2026 Alzheimer's disease (AD), a progressive neurodegenerative disorder, remains one of the greatest medical challenges because of its multifactorial nature. In recent years (2015–2025), benzothiazole‐based compounds have gained increasing attention as promising scaffolds for the development of anti‐Alzheimer agents. This comprehensive review focuses on the biological evaluation and structure–activity relationship (SAR) trends of benzothiazole derivatives targeting key enzymes and pathways implicated in AD. These include acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), β‐secretase (BACE1), monoamine oxidase A and B (MAO‐A, MAO‐B), receptor‐interacting protein kinase 1 (RIPK1), human DYRK1A (hDYRK1A), and human CLK1 ( h CLK1). Benzothiazole hybrids with diverse heterocyclic frameworks have been explored, and SAR analysis suggests that the presence of electron‐withdrawing substituents in the molecules significantly enhances their potency against Alzheimer's targets. Many of these compounds demonstrate strong in vitro activity, multitarget inhibition potential, and favorable interaction profiles in docking studies, highlighting their relevance as multitarget‐directed ligands. This review consolidates data from the last decade to provide insights into the structural features contributing to anti‐Alzheimer's activity and offers directions for the rational design of more selective, efficacious, and brain‐penetrant benzothiazole derivatives. Future research should focus on optimizing pharmacokinetic properties, improving blood–brain barrier permeability, and validating in vivo efficacy of the designed molecules. Overall, benzothiazole remains a valuable and versatile scaffold in the ongoing search for effective therapeutics for AD.
Design, synthesis and biological evaluation of some imidazo[1,2-a]pyridine derivatives as anti-tubercular agents: an in silico–in vitro approach Harnisha Patel, Afzal Nagani, Mirav Patel, Mitesh Patel, Mange Ram Yadav Journal of Biomolecular Structure and Dynamics, 2026 ]pyridine derivatives, 24 targets are the potential targets for treatment of Mtb infection. Among these 24 targets, 10 hub-targets were identified (TLR4, ICAM1, TLR9, STAT3, TNFRSF1A, ERBB2, CXCR3, ACE, IKBKG and NOS2) which were significantly involved in GO processes such as positive regulation of DNA-binding transcription factor activity, peptidyl-tyrosine phosphorylation, positive regulation of inflammatory response, mononuclear cell proliferation, regulation of hemopoiesis and cytokine production involved in inflammatory response and KEGG pathways such as pathways in Tuberculosis, NF-kappa B signalling, HIF-1 signalling PD-L1 expression, and PD-1 checkpoint pathway in cancer. Molecular docking and dynamics simulations confirmed the stable interactions of imidazo[1,2-a]pyridine derivatives with core target active sites, highlighting their potential as novel anti-TB drug candidates.
Pyrazolopyridine pyrimidone hybrids as potential DprE1 inhibitors, design, synthesis and biological evaluation as antitubercular agents Moksh Shah, Iva Patel, Pratik Khona, Harnisha Patel, Mange Ram Yadav, Afzal Nagani Scientific Reports, 2025 Tuberculosis (TB) remains a major global health challenge. This study presents the design, synthesis, and evaluation of some novel pyrazolo[3,4-b]pyridine-pyrimidone derivatives targeting Mycobacterium tuberculosis (Mtb). The compounds were assessed for anti-tubercular activity using the Microplate Alamar Blue Assay (MABA) against the Mtb H37Rv strain. Key derivatives (8 and 14) showed significant activity with minimum inhibitory concentration (MIC) values of 3.12 µg/mL, 12.5 µg/mL, respectively, comparable to the standard drugs and are nontoxic at their effective concentration as anti-TB agents. Molecular docking studies demonstrated strong binding interactions with DprE1 and Mtb-DHFR enzymes, suggesting inhibition of these critical proteins. Further computational analyses, including density functional theory (DFT) and molecular dynamics simulations, confirmed the binding stability of the compounds to the target proteins. Overall, these pyrazolo[3,4-b]pyridine-pyrimidone derivatives are potential leads for further development as future therapeutics for treating drug-resistant TB.
Oxadiazoles as multi-target therapeutic agents in Alzheimer’s Disease: A review of cholinesterase, MAO, β-Secretase, and Aβ aggregation inhibition Moksh Shah, Chanchal Singh, Mange Ram Yadav, Afzal Nagani Journal of Saudi Chemical Society, 2025 Alzheimer's disease (AD) is a complex neurodegenerative disorder with a poorly understood etiology and limited therapeutic options. It is a leading cause of global morbidity and mortality, with an economic burden surpassing that of HIV and cancer combined together. These challenges underscore the urgent need for devising novel and efficient therapeutic strategies. This review focuses on the potential of oxadiazole ring systems as privileged scaffolds to offer potential anti-AD agents. Recent advancements in their synthesis and structure–activity relationships (SAR) are discussed, with an emphasis on their activity against key AD targets, which include acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), β-secretase, monoamine oxidase B (MAO-B) and anti-oxidant potential. Additionally, molecular docking and molecular dynamics simulations are highlighted for their crucial role in understanding molecular binding interactions, predicting target protein–ligand complex stability, target specificity, and guiding the optimization strategies for the designing of potentially active anti-AD agents. Integration of these approaches demonstrates the immense potential of oxadiazoles in addressing the multifactorial etiology of AD and advancing the discovery of more effective treatments.
Design, Synthesis, and Biological Evaluation of Natural Carbolic Acid-Pyrazinamide Hybrids as Antimicrobial Agents Kripa Patel, Afzal Nagani, Moksh Shah, Khyati Patel Chemistryselect, 2025 Antimicrobial resistance (AMR) is an escalating global concern, calling for innovative approaches to combat resistant pathogens. This study reports the design, synthesis, and characterization of natural carbonic acid–pyrazinamide derivatives, focusing on compounds 6 and 7. The molecules were obtained via a molecular hybridization strategy employing acid–amine coupling, followed by deprotection steps, and their structures were confirmed using 1H NMR, 13C NMR, and HR‐MS analyses. Using the broth dilution method, compound 6 exhibited promising activity against P. aeruginosa (MIC: 62.5 µg/mL), whereas compound 7 showed similar efficacy against E. coli (MIC: 62.5 µg/mL), comparable to that of standard treatments. Molecular docking revealed strong binding interactions with key microbial targets, 14α‐demethylase and DHFR, indicating potential inhibition of these targets. Additional computational studies, including density functional theory (DFT) and molecular dynamics (MD) simulations, further supported the stability and binding strengths of these compounds. Overall, compound 7 emerged as the most potent candidate, both biologically and computationally, highlighting its potential as a lead scaffold for antimicrobial resistance.
