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Preliminary insight on diarylpentanoids as potential antimalarials: In silico, in vitro pLDH and in vivo zebrafish toxicity assessment.
Ramli, Amirah Hani; Swain, Puspanjali; Mohd Fahmi, Muhammad Syafiq Akmal; Abas, Faridah; Leong, Sze Wei; Tejo, Bimo Ario; Shaari, Khozirah; Ali, Amatul Hamizah; Agustar, Hani Kartini; Awang, Rusdam; Ng, Yee Ling; Lau, Yee Ling; Md Razali, Mohammad Aidiel; Mastuki, Siti Nurulhuda; Mohmad Misnan, Norazlan; Mohd Faudzi, Siti Munirah; Kim, Cheol-Hee.
Afiliación
  • Ramli AH; Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia.
  • Swain P; Department of Biology, Chungnam National University, Daejeon, 34134, South Korea.
  • Mohd Fahmi MSA; Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia.
  • Abas F; Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia.
  • Leong SW; Department of Food Science, Faculty of Food Science & Technology, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
  • Tejo BA; Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
  • Shaari K; Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
  • Ali AH; Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia.
  • Agustar HK; Department of Earth Sciences and Environment, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, 43600, Selangor, Malaysia.
  • Awang R; Department of Earth Sciences and Environment, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, 43600, Selangor, Malaysia.
  • Ng YL; UPM - MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
  • Lau YL; Department of Parasitology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
  • Md Razali MA; Department of Parasitology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
  • Mastuki SN; School of Graduate Studies, Management & Science University, 40100, Shah Alam, Malaysia.
  • Mohmad Misnan N; Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia.
  • Mohd Faudzi SM; Department of Biological Sciences and Biotechnology, Faculty of Science & Technology, Universiti Kebangsaan Malaysia, Bangi, 43600, Selangor, Malaysia.
  • Kim CH; Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, 40170, Shah Alam, Selangor Darul Ehsan, Malaysia.
Heliyon ; 10(5): e27462, 2024 Mar 15.
Article en En | MEDLINE | ID: mdl-38495201
ABSTRACT
Malaria remains a major public health problem worldwide, including in Southeast Asia. Chemotherapeutic agents such as chloroquine (CQ) are effective, but problems with drug resistance and toxicity have necessitated a continuous search for new effective antimalarial agents. Here we report on a virtual screening of ∼300 diarylpentanoids and derivatives, in search of potential Plasmodium falciparum lactate dehydrogenase (PfLDH) inhibitors with acceptable drug-like properties. Several molecules with binding affinities comparable to CQ were chosen for in vitro validation of antimalarial efficacy. Among them, MS33A, MS33C and MS34C are the most promising against CQ-sensitive (3D7) with EC50 values of 1.6, 2.5 and 3.1 µM, respectively. Meanwhile, MS87 (EC50 of 1.85 µM) shown the most active against the CQ-resistant Gombak A strain, and MS33A and MS33C the most effective P. knowlesi inhibitors (EC50 of 3.6 and 5.1 µM, respectively). The in vitro cytotoxicity of selected diarylpentanoids (MS33A, MS33C, MS34C and MS87) was tested on Vero mammalian cells to evaluate parasite selectivity (SI), showing moderate to low cytotoxicity (CC50 > 82 µM). In addition, MS87 exhibited a high SI and the lowest resistance index (RI), suggesting that MS87 may exert effective parasite inhibition with low resistance potential in the CQ-resistant P. falciparum strain. Furthermore, the in vivo toxicity of the molecules on early embryonic development, the cardiovascular system, heart rate, motor activity and apoptosis were assessed in a zebrafish animal model. The overall results indicate the preliminary potential of diarylpentanoids, which need further investigation for their development as new antimalarial agents.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Heliyon Año: 2024 Tipo del documento: Article País de afiliación: Malasia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Heliyon Año: 2024 Tipo del documento: Article País de afiliación: Malasia Pais de publicación: Reino Unido