Synthesis, biological assessment, and computational investigations of nifedipine and monastrol analogues as anti-leishmanial major and anti-microbial agents.
ADMET
Amastigote
Hantzsch reaction
Molecular docking
Molecular dynamics simulation
Promastigote
Journal
Molecular diversity
ISSN: 1573-501X
Titre abrégé: Mol Divers
Pays: Netherlands
ID NLM: 9516534
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
01
09
2022
accepted:
11
11
2022
medline:
13
11
2023
pubmed:
24
11
2022
entrez:
23
11
2022
Statut:
ppublish
Résumé
Leishmaniasis includes a range of parasitic diseases caused by numerous types of the protozoan kinetoplastid parasite. Fungal and bacterial pathogens have led to infectious illnesses causing some main public health problem in current years. A series of dihydropyridine and tetrahydropyrimidine derivatives having fluoro, bromo, and nitro substituents at para-phenyl ring on C4 of dihydropyridine and tetrahydropyrimidine rings were synthesized. Then, anti-leishmanial and antimicrobial potencies of compounds were assessed. All compounds were synthesized via Hantzsch and Biginelli reactions. All derivatives were evaluated for their anti-leishmanial and antimicrobial activities. Moreover, docking and molecular dynamics simulation calculations of the compounds in PRT1 binding site were performed to report the results of anti-leishmanial and antimicrobial activities. Compounds 4a and 4b showed the highest anti-amastigote and anti-promastigote activities. Compound 4a revealed the highest antimicrobial activity against E. coli, P. aeruginosa, and C. albicans strains. In addition, compound 4c showed the highest activity against S. aureus. The fluoro, bromo, and nitro substituents in para-position of phenyl group at C4 of dihydropyridine and tetrahydropyrimidine moieties as well as the bulk and length of the chain linking to the ester moieties are essential for anti-leishmanial and anti-microbial activities of these derivatives. Low cytotoxicity was shown by most of derivatives against macrophages. The molecular docking studies were in agreement with in vitro assay. Moreover, hydrogen binds, RMSF, RMSD, and Rg, strongly showed the steady binding of 4a and 4b compounds in PRT1 active site.
Identifiants
pubmed: 36417095
doi: 10.1007/s11030-022-10569-4
pii: 10.1007/s11030-022-10569-4
doi:
Substances chimiques
Nifedipine
I9ZF7L6G2L
monastrol
6BSM97YZ8G
Anti-Infective Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2555-2575Subventions
Organisme : Ardabil University of Medical Sciences
ID : IR.ARUMS.REC.1398.092
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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