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Unveiling the Efficacy of Sesquiterpenes from Marine Sponge Dactylospongia elegans in Inhibiting Dihydrofolate Reductase Using Docking and Molecular Dynamic Studies.
Omar, Abdelsattar M; Mohammad, Khadijah A; Sindi, Ikhlas A; Mohamed, Gamal A; Ibrahim, Sabrin R M.
Afiliación
  • Omar AM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  • Mohammad KA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
  • Sindi IA; Center for Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  • Mohamed GA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  • Ibrahim SRM; Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Molecules ; 28(3)2023 Jan 29.
Article en En | MEDLINE | ID: mdl-36770958
Dihydrofolate reductase (DHFR) is a crucial enzyme that maintains the levels of 5,6,7,8-tetrahydrofolate (THF) required for the biological synthesis of the building blocks of DNA, RNA, and proteins. Over-activation of DHFR results in the progression of multiple pathological conditions such as cancer, bacterial infection, and inflammation. Therefore, DHFR inhibition plays a major role in treating these illnesses. Sesquiterpenes of various types are prime metabolites derived from the marine sponge Dactylospongia elegans and have demonstrated antitumor, anti-inflammation, and antibacterial capacities. Here, we investigated the in silico potential inhibitory effects of 87 D. elegans metabolites on DHFR and predicted their ADMET properties. Compounds were prepared computationally for molecular docking into the selected crystal structure of DHFR (PDB: 1KMV). The docking scores of metabolites 34, 28, and 44 were the highest among this series (gscore values of -12.431, -11.502, and -10.62 kcal/mol, respectively), even above the co-crystallized inhibitor SRI-9662 score (-10.432 kcal/mol). The binding affinity and protein stability of these top three scored compounds were further estimated using molecular dynamic simulation. Compounds 34, 28, and 44 revealed high binding affinity to the enzyme and could be possible leads for DHFR inhibitors; however, further in vitro and in vivo investigations are required to validate their potential.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Poríferos / Sesquiterpenos / Antagonistas del Ácido Fólico Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Arabia Saudita Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Poríferos / Sesquiterpenos / Antagonistas del Ácido Fólico Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Arabia Saudita Pais de publicación: Suiza