2. Academic Validation
  3. Cytotoxic leuconoxine-type diazaspiroindole alkaloids isolated from Cryptolepis dubia

Cytotoxic leuconoxine-type diazaspiroindole alkaloids isolated from Cryptolepis dubia

  • Bioorg Med Chem Lett. 2024 Mar 15:101:129650. doi: 10.1016/j.bmcl.2024.129650.
Yulin Ren 1,  Elizabeth N Kaweesa 2,  Joshua M Henkin 2,  Kongmany Sydara 3,  Mouachanh Xayvue 3,  Pankaj Pandey 4,  Amar G Chittiboyina 4,  Zulfiqar Ali 4,  Daneel Ferreira 5,  Djaja D Soejarto 6,  Joanna E Burdette 2,  A Douglas Kinghorn 7
Affiliations

Affiliations

  • 1 Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
  • 2 Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, United States.
  • 3 Institute of Traditional Medicine, Ministry of Health, Vientiane, Lao Democratic People's Republic.
  • 4 National Center for Natural Products Research, University of Mississippi, University, MS 38677, United States.
  • 5 National Center for Natural Products Research, University of Mississippi, University, MS 38677, United States; Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, United States.
  • 6 Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, United States; Science and Education, Field Museum of Natural History, Chicago, IL 60605, United States.
  • 7 Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States. Electronic address: [email protected].
PMID: 38341161 DOI: 10.1016/j.bmcl.2024.129650
Abstract

Two leuconoxine-type diazaspiroindole Alkaloids, the known compound, (+)-melodinine E (1), and its new analogue, (+)-11-chloromelodinine E (2), were isolated from the stems of Cryptolepis dubia (Burm.f.) M.R. Almeida (Apocynaceae), collected in Laos. The chemical structures of these compounds were determined by analysis of their spectroscopic data and by comparison of these data with literature values, of which the molecular structure of 1 has been determined previously by analysis of its single-crystal X-ray diffraction data. The absolute configurations of 1 and 2 have been defined by their experimental and simulated electronic circular dichroism (ECD) spectroscopic data and supported by 1H and 13C NMR-based DP4+ probability analysis and specific rotation calculations. When tested against a small panel of human Cancer cell lines, these two compounds exhibited selective cytotoxicity toward OVCAR3 human ovarian Cancer cells.

Keywords

Absolute configuration; Cryptolepis dubia; Leuconoxine-type diazaspiroindole alkaloids; Melodinine E; Selective cytotoxicity.

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