2. Academic Validation
  3. Synthesis and antiviral activity of thiazolyl hydrazones against dengue virus

Synthesis and antiviral activity of thiazolyl hydrazones against dengue virus

  • Bioorg Med Chem Lett. 2025 Oct 10:130:130436. doi: 10.1016/j.bmcl.2025.130436.
Mohd Usman Mohd Siddique 1,  Deepak Shilkar 2,  Vasavi Garisetti 3,  Sheikh Murtuja 4,  Suzanne Kaptein 5,  Pieter Leyssen 5,  Johan Neyts 5,  Vinay N Basavanakatti 6,  Subodh Mondal 7,  Susanta Kumar Mondal 8,  Gayathri Dasararaju 3,  Velmurugan Devadasan 9,  Barij Nayan Sinha 2,  Venkatesan Jayaprakash 10
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Mesra, Ranchi 835215, JH, India; Department of Pharmaceutical Chemistry, Shri Vile Parle Kalevani Mandal's Institute of Pharmacy, Dhule 424001, MH, India.
  • 2 Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Mesra, Ranchi 835215, JH, India.
  • 3 Center for Advanced Studies in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600025, TN, India.
  • 4 Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Mesra, Ranchi 835215, JH, India; Department of Pharmaceutical Technology, School of Health and Medical Sciences, Adamas University, Kolkata 700126, WB, India.
  • 5 Department of Microbiology, Immunology and Transplantation, Virology, Antiviral Drug & Vaccine Research Group, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
  • 6 Adgyl Lifesciences Pvt Ltd., Bengaluru 560058, KA, India.
  • 7 Eurofins Advinus BioPharma Services India Pvt Ltd., Bengaluru 560058, KA, India.
  • 8 TCG Lifesciences Pvt. Ltd, Block-EP&GP, BIPL, Tower-B, Saltlake, Sector-V, Kolkata 700091, WB, India.
  • 9 Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203, TN, India.
  • 10 Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Mesra, Ranchi 835215, JH, India. Electronic address: venkatesanj@bitmesra.ac.in.
PMID: 41077226 DOI: 10.1016/j.bmcl.2025.130436
Abstract

Our group has previously reported on (E)-4-(1-(2-(5-(4-chlorophenyl)thiazol-2-yl)hydrazono)ethyl)phenol (3a) as an Antiviral agent against DENV with an EC50 of 1.32 μM. In this study, we present the X-ray crystallographic structure and in vitro ADME profile of compound 3a. Additionally, to optimize 3a, we synthesized four derivatives (3b-3e) using an active analogue approach. The newly synthesized and characterized compounds were screened for Antiviral activity against DENV via a virus reduction assay (RT-qPCR). Among them, compound 3c emerged as the most potent, with an EC50 of 0.01 μM and a selectivity index (SI) of 200. This compound was found to be 132 times more potent than 3a, although its toxicity was 63 times higher than that of 3a. Despite this, its selectivity index was twofold higher than that of compound 3a. In vitro permeability and metabolic stability studies showed that compound 3a exhibited permeability issues but demonstrated metabolic stability in both rat and human liver microsomes. In vivo pharmacokinetic studies in male rats revealed a bioavailability (F) of 6 % and a half-life (T1/2) of 1.75 h for compound 3a. The in vivo pharmacokinetic results for compound 3c suggest that it may require an appropriate formulation strategy to enhance its pharmacokinetic parameters.

Keywords

Antiviral activity; Dengue; In-vitro ADME; In-vivo PK studies; Molecular dynamics; Thiazoles.

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