Design, synthesis, and biological profiling of fluorinated cannabidiol and cannabigerol derivatives as promising therapeutic agents Ferenc Dániel Petróczi, Angéla Tótik, Miklós Bege, József Király, Erzsébet Szabó, Zsuzsanna Szabó, Nikoletta Dobos, Rasha Ghanem Kattoub, Charu Upadhyay, Eszter Ostorházi, Jan Hodek, Jan Weber, József Arany, Dorottya Ádám, Christos C. Zouboulis, Attila Oláh, István Bajza, Árpád Tósaki, Gábor Halmos, Brijesh Rathi, Pál Herczegh, Anikó Borbás, Ilona Bereczki Journal of Cannabis Research, 2026 Background Cannabidiol (CBD) and cannabigerol (CBG) are non-psychotropic phytocannabinoids that have significant, broad-spectrum therapeutic potential in a variety of pharmacological areas, but their unfavorable pharmacokinetics, such as extensive first-pass metabolism and low bioavailability, hinder their effective medical applications. Therefore, there is a great need for appropriate chemical modifications to improve their physicochemical properties. Incorporation of fluorine atom(s) at appropriate positions often improves the metabolic stability of the parent compound, increasing its bioavailability, and enhances its binding affinity to therapeutic targets, making fluorine a highly valuable element in modern drug development. Furthermore, amino functional groups may improve the water solubility and bioavailability of the compounds. Building on these principles, our strategy focused on introducing groups containing mono-, di-, and trifluoroethylamine or fluorinated aniline moieties into cannabinoids to improve their pharmacokinetic and pharmacological profiles. Methods Mannich-type reaction was applied, using commercially available 2-fluoroethylamine, 2,2-difluoroethylamine, 2,2,2-trifluoroethylamine, 3-fluoroaniline and 4-fluoroaniline as reagents. One or two oxazine rings with fluorine-containing side chains were condensed to the aromatic core of the cannabinoids, and the formation of mono- or disubstituted derivatives was controlled by the appropriate choice of reaction conditions. The biological activity of the derivatives was investigated in various relevant fields. Results and conclusion Our findings indicate that aliphatic modifications positively influence pharmacokinetic parameters, including absorption, in contrast to aromatic groups, which increase lipophilicity and lead to decreased bioavailability. Among the modifications, the monosubstituted derivatives containing a single oxazine ring with an aliphatic fluorine-containing side chain, especially the mono- and trifluoroethyl moieties, proved to be the most promising. These modifications appeared particularly advantageous in the CBG series compared to the properties of the CBG parent compound. This may suggest that the presence of a phenolic OH group is beneficial for biological activity. Some of the derivatives showed anticancer potential against various tumor cell lines, while others modulated sebaceous lipogenesis, and certain compounds exhibited a notable antimalarial effect.
Divergent Thioamide Synthesis via Umpolung C–N Bond Formation from Nitroethane in Aqueous Medium Padam Raj Bhatt, Ankush Gupta, Himanshi Sharma, Priyamvada Singh, Brijesh Rathi Journal of Organic Chemistry, 2026 We present a diverse synthesis of thioamides by installing elemental sulfur and amines in nitroethane via umpolung C–N bond formation. The uniqueness of this water-based protocol renders it more convenient for thioamide synthesis at room temperature. These mild reaction conditions ensure wide functional group tolerance, facilitating late-stage functionalization of drug scaffolds, including intermediates relevant to active pharmaceutical ingredient (API) synthesis.
Hydroxyethylamine & phthalimide analogs restoring defects due to GNE dysfunction: rare disease therapeutic significance Shagun Singh, Meenakshi Bansal, Neha Sharma, Vikas Yadav, Fluencephila Mashangva, Jyoti Oswalia, Vaishali Gautam, Gagan Deep Jhingan, Naidu Subbarao, Brijesh Rathi, Ranjana Arya Molecular Medicine, 2025 Rare diseases refer to a group of neglected diseases with low prevalence that face challenges in diagnostics as well as therapeutics due to phenotypic heterogeneity and ineffective clinical trials. In this study, we evaluated two novel analogs of hydroxyethylamine & phthalimide (LTC-181 and LTC-1717) for their potential effect on the epimerase activity of mutant GNE proteins associated with GNE myopathy. GNE gene encodes a key bifunctional sialic acid biosynthetic enzyme, UDP-N-acetyl Glucosamine 2-epimerase/N-acetyl Mannosamine Kinase; GNE). The compounds have significantly increased the epimerase activity of r-F307C-GNE and r-A555V-GNE mutant proteins in vitro. Reduced GNE epimerase activity and sialic acid content in muscle cell-based model for GNE function (SKM-GNEHz) was increased by 2-fold after addition of these compounds. The proteomic study showed that the compounds affected cytoskeletal organization, autophagy and muscle atrophy. Also, treatment with analogs enhanced the cell viability of SKM-GNEHz cells with increased F-actin polymerization and cell migration, thereby, restoring GNE deficient function. Additionally, effect of these compounds was observed with enhanced autophagy and reduced muscle atrophy function in GNE deficient muscle cell. Docking and interaction studies showed that LTC-1717 stabilize GNE better than LTC-181, indicating better therapeutic potential. Overall, this study indicates that HEA-phthalimide analog could be promising leads for treating GNE myopathy.
Catalytic Advances and Emerging Strategies for Isoquinolin-1(2H)-One Synthesis: Reaction Scope and Mechanistic Perspectives Lucky Panwar, Shalini Verma, Manoj Kumar, Brijesh Rathi European Journal of Organic Chemistry, 2025 Isoquinolin‐1(2H)‐one is a core structure in many bioactive molecules, natural products, and advanced materials. Its efficient and sustainable synthesis has garnered significant attention in organic synthesis. This abstract highlights recent advancements in the synthesis of isoquinolin‐1(2H)‐one via metal‐catalyzed, metal‐free, photocatalytic, and electro‐catalytic methods. Transition metal catalysis, employing palladium, rhodium, ruthenium, cobalt, copper, etc. complexes, enables versatile cyclization and functionalization pathways. Metal‐free approaches leverage organo‐catalysts and green oxidants for milder, environmentally benign conditions. Photocatalysis utilizes visible‐light‐active catalysts, enabling oxidative or reductive transformations with minimal waste. Electrocatalysis, offering tunable electrochemical conditions, facilitates CH activation and coupling strategies under ambient conditions. These methodologies display high regio‐ and chemo‐selectivity, broad substrate scope, and improved sustainability. Advances in these areas underscore the synergistic potential of combining catalytic techniques for the design of novel synthetic routes. This review serves as a foundation for developing more efficient and eco‐friendly approaches to constructing the isoquinolin‐1(2H)‐one scaffold.
Comparison of DNA extraction methods for COVID-19 host genetics studies Ronaldo Celerino da Silva, Suelen Cristina de Lima, Wendell Palôma Maria dos Santos Reis, Jurandy Júnior Ferraz de Magalhães, Ronaldo Nascimento de Oliveira Magalhães, Brijesh Rathi, Alain Kohl, Marcos André Cavalcanti Bezerra, Lindomar Pena Plos One, 2023
Biological activity of 1,2,3-triazole-2-amino-1,4-naphthoquinone derivatives and their evaluation as therapeutic strategy for malaria control Renata Maria Costa Souza, Lilian Maria Lapa Montenegro Pimentel, Laryssa Kathleen Mendonça Ferreira, Valéria Rêgo Alves Pereira, Aline Caroline Da Silva Santos, Willyenne Marília Dantas, Carla Jasmine Oliveira Silva, Ramayana Morais De Medeiros Brito, José Lucas Andrade, Valter Ferreira De Andrade-Neto, Ricardo Toshio Fujiwara, Lilian Lacerda Bueno, Valdemiro Amaro Silva Junior, Lindomar Pena, Celso Amorim Camara, Brijesh Rathi, Ronaldo Nascimento De Oliveira European Journal of Medicinal Chemistry, 2023
Deciphering the Role of c-MET in Metabolic Reprogramming of Head and Neck Squamous Cell Carcinoma via In Silico Analysis Chemical Biology Letters, 2023
Morphological analysis of metabolically dysregulated spermatozoa using Artificial Intelligence based approach Journal of Integrated Science and Technology, 2023
Therapeutic Potential of Benzopyrones Against Antiparasitic Diseases Meenakshi Bansal, Pooja Kumari, Rajender Singh Malik, Maria Grishina, Devender Singh, Brijesh Rathi, Sumit Kumar Natural Product Based Drug Discovery Against Human Parasites Opportunities and Challenges, 2023
Corona virus SARS-CoV-2 disease COVID-19: Infection, prevention and clinical advances of the prospective chemical drug therapeutics Chemical Biology Letters, 2020
In silico identification of potent fda approved drugs against coronavirus covid-19 main protease: A drug repurposing approach Chemical Biology Letters, 2020
Review of Atypical Organometallic Compounds as Antimalarial Drugs Samuel K. Kwofie, Emmanuel Broni, Bismark Dankwa, Kweku S. Enninful, Joshua Teye, Cedar R. Davidson, Josephine B. Nimely, J. Chioma Orizu, Prakasha Kempaiah, Brijesh Rathi, Whelton A. Miller Journal of Chemistry, 2020
Tetrahedral Hydroxyethylamine: A Privileged scaffold in development of antimalarial agents Chemical Biology Letters, 2014
Potentials of hydrogels in cancer therapy Prem Prakash Sharma, Ravindra Kumar, Anil K Singh, Brajendra K Singh, Ajay Kumar, Brijesh Rathi Current Cancer Therapy Reviews, 2014
Rauvolfia serpentina L. Benth. ex kurz.: Phytochemical, pharmacological and therapeutic aspects International Journal of Pharmaceutical Sciences Review and Research, 2013
