Title:One-Pot Synthesis of Novel Hydrazono-1,3-Thıazolıdın-4-One Derivatives
as Anti-HIV and Anti-Tubercular Agents: Synthesıs, Bıologıcal Evaluatıon,
Molecular Modelling and Admet Studıes
Volume: 20
Issue: 3
Author(s): Mohammad Arif Pasha, Sumanta Mondal*, Naresh Panigrahi, Gauri Shetye, Rui Ma, Scott G. Franzblau, Yong-Tang Zheng and Sankaranarayanan Murugesan
Affiliation:
- Department of Pharmaceutical Chemistry, GITAM Institute of Pharmacy,
Rushikonda, GITAM (Deemed to be University), Visakhapatnam-530045, Andhra Pradesh, India
Keywords:
Hydrazono 1, 3-thiazolidin-4-one, H37Rv, anti-HIV, anti-tubercular, ADMET.
Abstract:
Background: The necessity for newer anti-HIV and anti-tubercular medications has arisen as a
result of the prevalence of opportunistic infections caused by HIV (human immunodeficiency virus).
Objective: A series of ten new hydrazono 1,3-thiazolidin-4-one derivatives were synthesized in one-pot
and evaluated for anti-HIV and anti-tubercular activities. Molecular Docking was accomplished with
HIV-1 reverse transcriptase protein (PDB ID: 1REV) and Mycobacterium Tuberculosis (M. tuberculosis)
H37Rv protein (PDB ID: 2YES) receptors along with drug-likeness and ADMET properties.
Methods: One-pot synthesis of hydrazono 1,3-thiazolidin-4-one derivatives was carried out by ketones,
thiosemicarbazide and ethylchloroacetate with the catalyst of anhydrous sodium acetate. All
the synthesized compounds were characterized and evaluated for their in-vitro anti-HIV and also
evaluated for their in-vitro anti-tubercular activity against M. tuberculosis H37Rv. In-silico predicted
physicochemical parameters were done by MedChem DesignerTM software version 5.5 and ADMET
parameters by pkCSM online tool. Furthermore, molecular docking was performed with pyrx 0.8 by
autodock vina software.
Results: All the synthesized compounds were characterized and evaluated for their in-vitro anti-
HIV activity for inhibition of syncytia formation, which shows KTE1 with EC50 47.95 μM and Selectivity
Index (SI) of >4.17 and for inhibition of p24 antigen production EC50 was found to be
80.02 μM and SI of >2.49. The compounds were also evaluated for their in-vitro anti-tubercular activity
against M. tuberculosis H37Rv, in which KTE1 MIC values of 12.5μg/ml with SI of >4.0 and
cytotoxicity against Vero cell lines. In-silico predicted physicochemical parameters for synthesized
compounds which were found to be drug-like. Furthermore, docking has shown a good dock score
and binding energy with anti-HIV and anti-tubercular receptors.
Conclusion: From the novel synthesized molecules, none of the molecule is as effective as standards
for anti-HIV and anti-tubercular drugs and hence can be further explored for its potential activities.
Furthermore, derivatization was made to achieve more potent compounds for anti-HIV and
anti-tubercular drugs.
