2,3-Dihydroquinazolin-4(1H)-one as a New Class of Anti-Leishmanial Agents: A Combined Experimental and Computational Study

Crystals

Chenxi Wang¹  Song Xue¹  Muhammad Sarfraz¹  Humna Ellahi²  Muhammad Fayyaz ur Rehman³  Nargis Sultana³  Muhammad Jameel³  Muhammad Ilyas Tariq³  Shahzaib Akhter³  Fariha Kanwal⁴ 

[1] Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China;Department of Psychiatry, Lahore General Hospital, Lahore 54000, Pakistan;Institute of Chemistry, University of Sargodha, Sargodha 40100, Pakistan;Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 201620, China;

关键词: Leishmania;    Quinazoline;    anti-leishmanial agents;    MD simulations;   

DOI  :  10.3390/cryst12010044

来源: DOAJ

【 摘 要 】

Leishmaniasis is a neglected parasitic disease caused by various Leishmania species. The discovery of new protozoa drugs makes it easier to treat the disease; but, conventional clinical issues like drug resistance, cumulative toxicity, and target selectivity are also getting attention. So, there is always a need for new therapeutics to treat Leishmaniasis. Here, we have reported 2,3-dihydroquinazolin-4(1H)-one derivative as a new class of anti-leishmanial agents. Two derivatives, 3a (6,8-dinitro-2,2-disubstituted-2,3-dihydroquinazolin-4(1H)-ones) and 3b (2-(4-chloro-3-nitro-phenyl)-2-methyl-6,8-dinitro-2,3-dihydro-1H-quinazolin-4-one) were prepared that show promising in silico anti-leishmanial activities. Molecular docking was performed against the Leishmanial key proteins including Pyridoxal Kinase and Trypanothione Reductase. The stability of the ligand-protein complexes was further studied by 100 ns MD simulations and MM/PBSA calculations for both compounds. 3b has been shown to be a better anti-leishmanial candidate. In vitro studies also agree with the in-silico results where IC₅₀ for 3a and 3b was 1.61 and 0.05 µg/mL, respectively.

【 授权许可】

Unknown