Startseite Furanyl-Chalcones as antimalarial agent: synthesis, in vitro study, DFT, and docking analysis of PfDHFR inhibition
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Furanyl-Chalcones as antimalarial agent: synthesis, in vitro study, DFT, and docking analysis of PfDHFR inhibition

  • Fia Fathiana Wulan , Rachelio Clorozenta Pranaya , Jecky , Intan Nadira , Endang Astuti , Niko Prasetyo und Tutik Dwi Wahyuningsih ORCID logo EMAIL logo
Veröffentlicht/Copyright: 27. März 2025
Pure and Applied Chemistry
Aus der Zeitschrift Pure and Applied Chemistry Band 97 Heft 6

Abstract

Malaria continues to pose a significant threat to global health, demanding the development of novel antimalarial agents. This study investigated the antimalarial potential of eleven (11) furanyl-chalcone derivatives synthesized from two distinct furan sources: 2-acetylfuran and furfuraldehyde with Claisen–Schmidt condensation under base conditions, and successfully synthesized target compound with yields ranging from 67 % to 94 %. Structural characterization was achieved using spectroscopic techniques, including NMR, IR, and GC-MS. Our findings revealed that compounds derived from 2-acetylfuran exhibited superior antimalarial activity compared to their furfuraldehyde counterparts. Compounds B1 and B4 demonstrated the most promising activity with IC50 values of 1.01 μM and 1.04 μM, respectively against P.falciparum FCR-3 strain. Our analysis revealed that B4 forms a stable hydrogen bond with Ser108 in the active site of wild-type PfDHFR, with a binding affinity of −6.7 kcal/mol. Importantly, this interaction was preserved even in the presence of a mutation at this residue, with B4 forming a hydrogen bond with Asn108 in the mutant enzyme, exhibiting a binding affinity of −7.0 kcal/mol. This suggests that B4 has the potential to overcome pyrimethamine resistance. Further analysis, utilizing DFT calculations and MEP, identified B4 as the most reactive compound within the series. The reactive site was located in the carbonyl group, with enhanced reactivity attributed to the presence of the electron-rich furan ring and the ortho-methoxy substituent.

Keywords: Antimalarial activity; density functional theory (DFT); furan-based chalcone; ICYC 2024; PfDHFR inhibition
Corresponding author: Tutik Dwi Wahyuningsih, Department of Chemistry, Faculty of Mathematics and Natural Sciences Universitas Gadjah Mada, Yogyakarta, 42124, Indonesia, e-mail:
Article note: A collection of invited papers based on presentations at the 9th International Conference for Young Chemists (ICYC 2024) held on 9–11 Oct 2024 in Penang, Malaysia.

Funding source: Kementerian Pendidikan, Kebudayaan, Riset, dan Teknologi Indonesia

Award Identifier / Grant number: 2081/UN1/DITLIT/PT.01.03/2024

Acknowledgments

Special appreciation is extended to the Austrian–Indonesian Centre for Computational Chemistry for providing access to Gaussian 09.

  1. Research ethics: The Medical and Health Research Ethics Committee (MHREC), Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada – Dr. Sardjito General Hospital, provided ethical clearance for the antimalarial test, with the reference number KE/FK/1421/EC/2022.

  2. Informed consent: Not applicable.

  3. Author contributions: FFW: Data Collection or Processing, Literature Search, Writing RCP: Data Collection or Processing J: Data Collection or Processing, IN: Data Collection or Processing EA: Design, Writing NP: Design, Writing TDW: Concept, Design, Literature Search, Writing.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: The authors gratefully acknowledge the Indonesian Ministry of Higher Education, Science, and Technology for the Pendidikan Magister Menuju Doktor Untuk Sarjana Unggul (PMDSU) scholarship awarded to Fia Fathiana Wulan (contract number 2081/UN1/DITLIT/PT.01.03/2024).

  7. Data availability: Not applicable.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/pac-2024-0330).

Received: 2024-11-21
Accepted: 2025-02-10
Published Online: 2025-03-27
Published in Print: 2025-06-26

© 2025 IUPAC & De Gruyter

Artikel in diesem Heft

  1. Frontmatter
  2. In this issue
  3. Preface
  4. Preface: 9th International Conference for Young Chemists (ICYC) 2024
  5. Research Articles
  6. Doping TiO2 with Cu from electroplating wastewater for remarkable improvement of its activity under visible light for E. coli bacterial disinfection in water
  7. Investigating the potential of prenylated and geranylated acylphloroglucinol-based xanthenones as potent soybean 15-lipoxygenase inhibitors: a combined in vitro and in silico approach
  8. Intelligent food packaging from Ganyong starch (Canna Edulis Kerr.) modified with nanocellulose from corn husk (Zea mays) and curcumin as bioindicator
  9. Evaluation of 2-(1H-1,2,3-triazol-1-yl) acetic acid derivatives as potential human hypoxia-inducible factor (HIF) prolyl hydroxylase domain-2 (PHD2) inhibitors
  10. Microparticles zerumbone from Zingiber zerumbet rhizome in chitosan modified oleic acid
  11. Enhanced visible photocatalytic degradation of diclofenac by ultrasound-assisted prepared C and N co-doping TiO2
  12. Enhanced stability and permeability of graphene oxide nanocomposite membranes via glycine and diglycine cross-linking
  13. Furanyl-Chalcones as antimalarial agent: synthesis, in vitro study, DFT, and docking analysis of PfDHFR inhibition
https://doi.org/10.1515/pac-2024-0330
Schlagwörter für diesen Artikel
Antimalarial activity; density functional theory (DFT); furan-based chalcone; ICYC 2024; PfDHFR inhibition

Artikel in diesem Heft

  1. Frontmatter
  2. In this issue
  3. Preface
  4. Preface: 9th International Conference for Young Chemists (ICYC) 2024
  5. Research Articles
  6. Doping TiO2 with Cu from electroplating wastewater for remarkable improvement of its activity under visible light for E. coli bacterial disinfection in water
  7. Investigating the potential of prenylated and geranylated acylphloroglucinol-based xanthenones as potent soybean 15-lipoxygenase inhibitors: a combined in vitro and in silico approach
  8. Intelligent food packaging from Ganyong starch (Canna Edulis Kerr.) modified with nanocellulose from corn husk (Zea mays) and curcumin as bioindicator
  9. Evaluation of 2-(1H-1,2,3-triazol-1-yl) acetic acid derivatives as potential human hypoxia-inducible factor (HIF) prolyl hydroxylase domain-2 (PHD2) inhibitors
  10. Microparticles zerumbone from Zingiber zerumbet rhizome in chitosan modified oleic acid
  11. Enhanced visible photocatalytic degradation of diclofenac by ultrasound-assisted prepared C and N co-doping TiO2
  12. Enhanced stability and permeability of graphene oxide nanocomposite membranes via glycine and diglycine cross-linking
  13. Furanyl-Chalcones as antimalarial agent: synthesis, in vitro study, DFT, and docking analysis of PfDHFR inhibition
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