Natural products as potential inhibitors of FLT3 for acute myeloid leukemia: HTVS, docking, and molecular dynamic simulation

• Autorzy: Salah Salsabeel , Sami Najat , Ali Sarah , Khalid Teemah-Alrahman , Alnajjar Radwan

Identyfikatory

DOI

10.58332/scirad2023v2i4a03

• Języki publikacji: EN

Abstrakty

EN

Cancer is one the most common health issues worldwide, with cancer-related mortality of 9.5 million in 2018, with an expectation to become 29.5 by 2040. Among others, acute myeloid leukemia (AML) is common among older people. FLT3 mutations are one of the most common genetic aberrations found in Acute Myeloid Leukemia and are associated with poor prognosis. Herein, we attempt to identify natural compounds as potential candidates to treat AML by targeting the FLT3 kinase domain using in silico approaches. The COCONUT database, which contains 407,270 natural compounds, was HTVS against the FLT3 kinase domain active site, and promising compounds were subject to molecular docking. Finally, frontier compounds were validated further using molecular dynamic simulation. In total, ten compounds were identified with docking scores higher than Quizartinib (-11.606 kcal/mol), with the best three compounds showing a docking score of -18.052, -15.772, and -16.767 kcal, respectively, and compound 2 showing excellent stability in molecular dynamic simulation.

Słowa kluczowe

EN

acute myeloid leukemia; drug design; anticancer; CADD; FLT3

PL

ostra białaczka szpikowa; projektowanie leków; terapia antynowotworowa; CADD; FLT3

• Wydawca: Radomskie Towarzystwo Naukowe
• Czasopismo: Scientiae Radices
• Rocznik: 2023
• Tom: Vol. 2, Iss. 4
• Strony: 325--346
• Opis fizyczny: Bibliogr. 23 poz., il. kolor., rys.

Twórcy

autor

Salah Salsabeel

• PharmD, Faculty of Pharmacy, Libyan International Medical University, Benghazi, Libya

autor

Sami Najat

• PharmD, Faculty of Pharmacy, Libyan International Medical University, Benghazi, Libya

autor

Ali Sarah

• PharmD, Faculty of Pharmacy, Libyan International Medical University, Benghazi, Libya

autor

Khalid Teemah-Alrahman

• PharmD, Faculty of Pharmacy, Libyan International Medical University, Benghazi, Libya

autor

Alnajjar Radwan

• PharmD, Faculty of Pharmacy, Libyan International Medical University, Benghazi, Libya
• Department of Chemistry, Faculty of Science, University of Benghazi, Benghazi, Libya

Bibliografia

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Uwagi

Opracowanie rekordu ze środków MNiSW, umowa nr SONP/SP/546092/2022 w ramach programu "Społeczna odpowiedzialność nauki" - moduł: Popularyzacja nauki i promocja sportu (2024).