Integrated structure-guided computational design of novel substituted quinolizin-4-ones as Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors

Vyas, Vivek K.; Shukla, Tanvi; Tulsian, Kartik; Sharma, Manmohan; Patel, Shivani

doi:10.1016/j.compbiolchem.2022.107787

Cited by 7 publications

(7 citation statements)

References 41 publications

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“…In our previous work, we have provided the coverage of medicinal aspects of heterocycles as anti-malarial scaffolds published during 2016-2020. [29] In continuation to the ongoing efforts on the synthesis of heterocycles [30][31][32][33][34][35][36] as medicinally important scaffolds [37,38] or anti-malarial agents, [39][40][41][42] the present work provides the detail aspects of all the reported heterocycles reported in 2021 and 2022 for the interest of medicinal chemists working on anti-malarial drug development along with their pharmacophoric features, structure-activity relationships (SAR), potential against multi-drug resistant strains, mode of actions, in silico/ in vitro/ in vivo activity, if reported.…”

Section: Heterocycles As Privileged Scaffold Towards Anti-malarial Ag...mentioning

confidence: 99%

Biannual Account of Anti‐malarial Agents reported in 2021 and 2022: A Comprehensive Coverage

Dhameliya,

Patel,

Kathuria

et al. 2024

ChemistrySelect

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Malaria remains a severe infectious disease caused by Plasmodium parasites among the primarily afflicting impoverished populations. According to World Health Organization (WHO) report, there were an estimated 247 million malarial cases globally, resulting in approximately 6,19,000 fatalities. Particularly prevalent in tropical and subtropical regions, the development of drug resistance has exacerbated this public health challenge. Consequently, there has been a concrete effort to explore novel compounds with anti‐malarial properties. In continuation of our previous works, this review focuses on heterocyclic compounds documented in 2021 and 2022, including artemisinin, benzimidazole, benzofuran, β‐lactam, coumarin, furan, indole, morpholine, piperazine, pyrimidine, quinoline, triazole, etc. highlighting their efficacy, structural characteristics, in vitro and in vivo activities, among other relevant aspects for the broad interest of medicinal chemists working on the design and development of novel anti‐malarial agents.

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Section: Heterocycles As Privileged Scaffold Towards Anti-malarial Ag...mentioning

confidence: 99%

Biannual Account of Anti‐malarial Agents reported in 2021 and 2022: A Comprehensive Coverage

Dhameliya,

Patel,

Kathuria

et al. 2024

ChemistrySelect

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“…The figures 6d and 6e presented the plots of solvent assessable surface area (SASA) and HB, respectively within a suitable range of 490-538 nm 2 for ligand-Figure 5. BOILED egg model of hit compounds (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). BBB and GI permeability have been indicated by the yellow and colorless zones, respectively.…”

Section: Simulationsmentioning

confidence: 99%

“…The Biovia Discovery Studio 2021 was utilized to visualize and analyze docking interactions between proteins and ligands. [41] The 2-D structures of compounds (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) are provided in the supplementary material (Figures S1-S3).…”

Section: Molecular Dockingmentioning

confidence: 99%

“…Various physiochemical features of hits (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) and pyrimethamine (1) were investigated using Swiss ADME [44] and pkCSM, [46,45] including MW, number of HBD, number of HBA, Log P, and number of RB. Several criteria, including Ghose's rule, Lipinski's rule of 5, Veber's rule, Muegge's rule, and Egan's rule have been applied to the hits to check drug likeliness.…”

Section: Physicochemical Characteristics Admet Information and Drug L...mentioning

confidence: 99%

“…Physical and chemical analysis of the compounds(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) and currently used molecule, Pyrimethamine (1).…”

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confidence: 99%

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Investigation on Anti‐plasmodial Agents Against wild‐type PfDHFR Through In Silico Computational Tools

Parikh,

Pandya,

Salaria

et al. 2024

ChemistrySelect

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Malaria is the most severe and common parasitic infection, with P. falciparum responsible for the majority of cases and deaths each year. As anti‐malarial drug resistance continues to increase, novel compounds with anti‐ P. falciparum activity must be identified. In search of a new molecule to cure the resistant malarial parasite, a total of 1,70,269 ligands from the Asinex BioDesign library 2021.2 were virtually screened using AutoDock Vina against wild‐type P. falciparum dihydrofolate reductase‐thymidylate synthase (PfDHFR‐TS). The computational molecular modeling investigations indicated the discovery of seventeen new compounds (2‐18) with higher binding energy compared to the PfDHFR‐TS inhibitor, pyrimethamine (1). Furthermore, the study employing drug‐likeness criteria and their ADMET profile suggested that these hits were the most promising drug candidates due to higher absorption and druggability. Furthermore, GROMACS 2023.4 was used to perform the molecular dynamics simulations on the foremost compound (2) having sufficient stability, leading to a key step towards the search of novel PfDHFR‐TS inhibitors against malaria.

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A comprehensive review of synthetic strategies and SAR studies for the discovery of PfDHODH inhibitors as antimalarial agents. Part 1: triazolopyrimidine, isoxazolopyrimidine and pyrrole-based (DSM) compounds

Sharma,

Pandey,

Poli

et al. 2024

Bioorganic Chemistry

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Integrated structure-guided computational design of novel substituted quinolizin-4-ones as Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors

Cited by 7 publications

References 41 publications

Biannual Account of Anti‐malarial Agents reported in 2021 and 2022: A Comprehensive Coverage

Biannual Account of Anti‐malarial Agents reported in 2021 and 2022: A Comprehensive Coverage

Investigation on Anti‐plasmodial Agents Against wild‐type PfDHFR Through In Silico Computational Tools

A comprehensive review of synthetic strategies and SAR studies for the discovery of PfDHODH inhibitors as antimalarial agents. Part 1: triazolopyrimidine, isoxazolopyrimidine and pyrrole-based (DSM) compounds

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