Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 15 min ago
PreprintCC BYChemRxiv

Target breadth and mutation resilience in African-natural-product-inspired antimalarial chemotypes: a computational analysis

  • Myke Vital Sao Temgoua1
  • Jean-Pierre Tchapet Njafa1
  • Penabei Samafou2
  • Wilfred Fon Mbacham3
  • Serge Guy Nana Engo1
  1. 1Department of Physics, Faculty of Science, University of Yaoundé, P.O. Box 812, Yaoundé, Cameroon
  2. 2Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue Nord, Sherbrooke, QC, Canada, J1H 5N4
  3. 3Faculty of Science, University of Yaoundé, P.O. Box 812, Yaoundé, Cameroon
Open at sourcePDFDOICite

Abstract

Can target breadth and mutation resilience be evaluated as distinct, complementary properties when prioritizing antimalarial chemotypes from African natural-product-inspired chemical space? We addressed this question by linking chemical-space expansion to target-specific docking and a per-target resistance-resilience score (RRS), while keeping computational evidence separate from biological activity. A hybrid library of 65 856 molecules, generated from 396 African natural products and 454 synthetic antimalarial compounds, yielded 19 913 computationally prioritized synthesizable leads. A 17-member polypharmacology-oriented cohort was evaluated by AutoDock Vina against PfDHFR, PfCRT, PfClpP, and PfATP4 using target-specific structural anchors. All 68 candidate–target pairs passed the geometric pose-quality criterion, with scores ranging from −7.91 kcal/mol to −4.63 kcal/mol. Per-target RRS was calculated from separate PfDHFR (N51I, C59R, S108N, I164L) and PfCRT (K76T, K76A) mutant panels, excluding non-binding wild-type targets from the denominator. The cohort comprised six A*, five B, five C, and one D RRS profiles, spanning 68.2 to 111.7. Cross-metric associations were weak or non-significant after multiplicity correction: PNS–RRS ρ = −0.559, ACSI–RRS ρ = −0.132, and RRS–wild-type score ρ = −0.433. The resulting target profiles define testable hypotheses about chemotype breadth and mutation resilience; they do not establish potency, target engagement, or resistance circumvention.

Related

  1. Do topological and quantum-inspired molecularrepresentations add value? Evidence from Africannatural-product-inspired antimalarial chemical space
    Myke Vital Sao Temgoua, Jean-Pierre TCHAPET NJAFA, Serge Guy Nana Engo +2
    ChemRxivPreprintCC BYFull textGeneral chemistryChemRxiv
  2. Antileishmanial and Antimalarial Activities of Synthetic Marine Endoperoxides
    Lukas Montejo, Estelle Messe, Mélanie Hery +6
    HALPreprintLicence not statedFull textMicrobiologyOrganic chemistryHAL
  3. Evaluation of Different Chemotypes of Lavandula angustifolia Essential Oils as Phytobiotics for the Control of Clinical Escherichia coli Strains Isolated from Commercial Poultry Production
    Michalina Adaszyńska-Skwirzyńska, Małgorzata Dzięcioł, Sławomir Zych
    Molecules (Basel, Switzerland)Peer-reviewedCC BYFull textGeneral chemistryEurope PMCCrossref
  4. Estimand Divergence Between Static Docking and Molecular Dynamics as a Triage Filter for Antimalarial Leads
    Myke Vital SAO TEMGOUA, Jean-Pierre TCHAPET NJAFA, Penabei SAMAFOU +2
    ChemRxivPreprintCC BYFull textGeneral chemistryChemRxiv
  5. A Mixed-Micelle Capillary Electrophoresis Method for Fast Quality Screening of Antimalarial Drugs
    Hailekiros Gebretsadik Kidanemariam, Erwin Adams, Ann Van Schepdael
    MoleculesPeer-reviewedCC BY 4.0Analytical chemistryCrossref

Cite

BibTeXRIS
BibTeX
@misc{temgoua2026target,
  title = {{Target breadth and mutation resilience in African-natural-product-inspired antimalarial chemotypes: a computational analysis}},
  author = {Myke Vital Sao Temgoua and Jean-Pierre Tchapet Njafa and Penabei Samafou and Wilfred Fon Mbacham and Serge Guy Nana Engo},
  howpublished = {ChemRxiv},
  year = {2026},
  month = sep,
  doi = {10.26434/chemrxiv.15006437/v2},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15006437/v2},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Target breadth and mutation resilience in African-natural-product-inspired antimalarial chemotypes: a computational analysis
AU  - Myke Vital Sao Temgoua
AU  - Jean-Pierre Tchapet Njafa
AU  - Penabei Samafou
AU  - Wilfred Fon Mbacham
AU  - Serge Guy Nana Engo
PY  - 2026
DA  - 2026/09/08
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15006437/v2
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15006437/v2
AB  - Can target breadth and mutation resilience be evaluated as distinct, complementary properties when prioritizing antimalarial chemotypes from African natural-product-inspired chemical space? We addressed this question by linking chemical-space expansion to target-specific docking and a per-target resistance-resilience score (RRS), while keeping computational evidence separate from biological activity. A hybrid library of 65 856 molecules, generated from 396 African natural products and 454 synthetic antimalarial compounds, yielded 19 913 computationally prioritized synthesizable leads. A 17-member polypharmacology-oriented cohort was evaluated by AutoDock Vina against PfDHFR, PfCRT, PfClpP, and PfATP4 using target-specific structural anchors. All 68 candidate–target pairs passed the geometric pose-quality criterion, with scores ranging from −7.91 kcal/mol to −4.63 kcal/mol. Per-target RRS was calculated from separate PfDHFR (N51I, C59R, S108N, I164L) and PfCRT (K76T, K76A) mutant panels, excluding non-binding wild-type targets from the denominator. The cohort comprised six A*, five B, five C, and one D RRS profiles, spanning 68.2 to 111.7. Cross-metric associations were weak or non-significant after multiplicity correction: PNS–RRS ρ = −0.559, ACSI–RRS ρ = −0.132, and RRS–wild-type score ρ = −0.433. The resulting target profiles define testable hypotheses about chemotype breadth and mutation resilience; they do not establish potency, target engagement, or resistance circumvention.
ER  -