2. Academic Validation
  3. Pyridine-4(1 H)-one Alkaloids from Waltheria indica as Antitrypanosomatid Agents

Pyridine-4(1 H)-one Alkaloids from Waltheria indica as Antitrypanosomatid Agents

  • J Nat Prod. 2020 Nov 25;83(11):3363-3371. doi: 10.1021/acs.jnatprod.0c00671.
Sylvian Cretton 1 2,  Marcel Kaiser 3 4,  Soumana Karimou 5,  Samad N Ebrahimi 6,  Pascal Mäser 3 4,  Muriel Cuendet 1 2,  Philippe Christen 1 2
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, University of Geneva, 1211 Geneva 4, Switzerland.
  • 2 Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva 4, Switzerland.
  • 3 Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland.
  • 4 University of Basel, 4003 Basel, Switzerland.
  • 5 Plantasav, B.P. 10308 Niamey, Niger.
  • 6 Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran.
PMID: 33095014 DOI: 10.1021/acs.jnatprod.0c00671
Abstract

Twelve new pyridine-4(1H)-one derivatives, namely, 8-demethoxywaltherione F (1), waltheriones R-V (2, 6, 7, 10, and 11), 1-methoxywaltherione O (3), (S)-15-hydroxywaltherione G (4), (8R)-8-hydroxywaltherione M (5), (9S,13S)-2-hydroxymethylwaltherione C (8), (9S,10S,13S)-10-hydroxywaltherione C (9), and (S)-13-methoxywaltherione V (12), as well as melovinone (13) and 5'-methoxywaltherione A (14) were isolated from the CH2Cl2 extract of the aerial parts of Waltheria indica. Their chemical structures were determined by means of a comprehensive analysis including 1H NMR, DEPTQ, HSQC, HMBC, 1H-1H COSY, ROESY, and HRESIMS data. The absolute configurations were assigned via comparison of the experimental and calculated ECD data. In addition, the isolated constituents as well as the known waltheriones M-Q were evaluated for their in vitro antitrypanosomal activity. Compounds 2, 5, and 7 as well as waltheriones M, P, and Q showed potent growth inhibition toward Trypanosoma cruzi with IC50 values of 2.1, 0.8, 2.1, 1.3, 0.5, and 0.1 μM, respectively, and selectivity indices of >12, >33, >13, 5, 25, and 14. These findings further demonstrate that the waltheriones are a promising class of antichagasic compounds worthy of further investigations.

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