Insights into Structural Modifications of Valproic Acid and Their Pharmacological Profile
Manish Kumar Mishra,
Samiksha Kukal,
Priyanka Rani Paul,
Shivangi Bora,
Anju Singh,
Shrikant Kukreti,
Luciano Saso,
Karthikeyan Muthusamy,
Yasha Hasija,
Ritushree Kukreti
Affiliations
Manish Kumar Mishra
Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi 110007, India
Samiksha Kukal
Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi 110007, India
Priyanka Rani Paul
Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi 110007, India
Shivangi Bora
Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi 110007, India
Anju Singh
Nucleic Acids Research Lab, Department of Chemistry, University of Delhi (North Campus), Delhi 110007, India
Shrikant Kukreti
Nucleic Acids Research Lab, Department of Chemistry, University of Delhi (North Campus), Delhi 110007, India
Luciano Saso
Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy
Karthikeyan Muthusamy
Department of Bioinformatics, Alagappa University, Karaikudi 630004, Tamil Nadu, India
Yasha Hasija
Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, Delhi 110042, India
Ritushree Kukreti
Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi 110007, India
Valproic acid (VPA) is a well-established anticonvulsant drug discovered serendipitously and marketed for the treatment of epilepsy, migraine, bipolar disorder and neuropathic pain. Apart from this, VPA has potential therapeutic applications in other central nervous system (CNS) disorders and in various cancer types. Since the discovery of its anticonvulsant activity, substantial efforts have been made to develop structural analogues and derivatives in an attempt to increase potency and decrease adverse side effects, the most significant being teratogenicity and hepatotoxicity. Most of these compounds have shown reduced toxicity with improved potency. The simple structure of VPA offers a great advantage to its modification. This review briefly discusses the pharmacology and molecular targets of VPA. The article then elaborates on the structural modifications in VPA including amide-derivatives, acid and cyclic analogues, urea derivatives and pro-drugs, and compares their pharmacological profile with that of the parent molecule. The current challenges for the clinical use of these derivatives are also discussed. The review is expected to provide necessary knowledgebase for the further development of VPA-derived compounds.