Title:Pyrazole based Furanone Hybrids as Novel Antimalarial: A Combined
Experimental, Pharmacological and Computational Study
Volume: 22
Issue: 1
Author(s): Deepika Choudhary, Isha Rani, Jyoti Monga, Rajat Goyal, Asif Husain, Prabha Garg and Sukhbir Lal Khokra*
Affiliation:
- Institute of Pharmaceutical Sciences, Kurukshetra University Kurukshetra-136119, Haryana, India
Keywords:
In-silico, furanones, pyrazole, antimalarial, PfLDH, synthesis, docking studies.
Abstract:
Background: Malaria parasite strains are resistant to the therapeutic effect of prophylactics
medicines presently available. This resistance now poses a significant challenge to researchers
to beat malaria parasitic infections. Strategies such as investigating newer hybrid chemical
entities and specified drug targets may help us spot new efficient derivatives that bind to the
parasites in a more specific manner and inhibit their growth.
Objective: To scientifically perform the experimental, pharmacological, and computational studies
of pyrazole-based furanone hybrids as novel antimalarial agents.
Methods: A series of new furanone-based pyrazole derivatives were synthesized and investigated
as potential antimalarial agents by performing in vitro antimalarial activity. To get further optimization,
these synthesized derivatives were virtually screened based on ADME-T filters, and molecular
docking studies were also accomplished on the crystal structures of Plasmodium falciparum
lactate dehydrogenase (PfLDH). Furthermore, the in-silico prediction was supported by performing
an LDH assay.
Results: The docking data suggested that the designed hybrid of furanone-pyrazole may act as
PfLDH inhibitors. It was found that the results of experimental in vitro antimalarial activity and in
silico analysis correlate well to each other to a good extent. The compounds (7d), (7g), and (8e)
were found to be the most potent derivatives with IC50 values of 1.968, 1.983, and 2.069 μg/ml, respectively.
Conclusion: From the results, it may be concluded that compounds that are active in low doses
might be adopted as a lead compound for the development of more active antimalarial agents. The
synthesized compounds (7d), (7g), and (8e) exhibited good antimalarial activity with PfLDH inhibition.
The best compounds can be explored further in the future for designing the potent inhibitors
of PfLDH as new potent antimalarial agents.
