Cyclodepsipeptides: Isolation from Endophytic Fungi of Sarcophyton ehrenbergi and Verification of Their Larvicidal Activity via In-Vitro and In-Silico Studies

Mar Drugs. 2022 May 18;20(5):331. doi: 10.3390/md20050331.

Abstract

Culex pipiens mosquitoes are vectors to many viruses and can transmit diseases such as filariasis and avian malaria. The present study evaluated the larvicidal activity of marine-derived endophytic fungi Aspergillus nomius and Aspergillus flavus from the soft coral Sarcophyton ehrenbergi along with two known cyclodepsipeptide compounds, scopularide A (1) and B (2), isolated from A. flavus extract, against third-instar larvae of C. pipiens, using distilled water as a negative control and toosenedanin as a positive control. The structures of the isolated compounds were confirmed by various spectroscopic analyses. The lethal concentrations (LC50 and LC90) were calculated by probit analysis. Scopularide A was the most potent after 96 h treatment, with LC50 and LC90 values of 58.96 and 994.31 ppm, respectively, and with 82.66% mortality at a concentration of 300 ppm. To unravel the biochemical mechanism of the tested extracts and compounds, their effects against protease, chitinase, phenoloxidases and lipase enzymes from the whole-body tissue of C. pipiens were evaluated after 72 h treatment at LC50 dose. Superior activity was observed for A. flavus extract against all tested enzymes. A molecular docking study was conducted for scopularide A and B on the four tested enzymes, to further verify the observed activity. Results revealed good binding affinities for both compounds as compared to the docked ligands, mainly via a number of hydrogen bonds. This was the first study to report the isolation of endophytic fungi A. flavus and A. nomius from the marine soft coral S. ehrenbergi. The endophytic fungal extract of A. flavus was found to be a promising source for a natural larvicidal agent against C. pipiens populations.

Keywords: Culex pipiens; Sarcophyton ehrenbergi; chitinase; docking; endophytes; lipase; phenoloxidases; protease.

MeSH terms

  • Animals
  • Anthozoa*
  • Depsipeptides* / pharmacology
  • Fungi
  • Insecticides*
  • Molecular Docking Simulation
  • Mosquito Vectors
  • Plant Extracts / chemistry

Substances

  • Depsipeptides
  • Insecticides
  • Plant Extracts

Grants and funding

This work was supported by the Ministry of Science and Technology, Taiwan (MOST 108-2320-B-037-022-MY3, 109-2927-I-037-502, 106-2811-B-037-025, 110-2811-B-037-518), awarded to Dr. Fang-Rong Chang; Kaohsiung Medical University Research Center, Taiwan (KMU-TC108A0) and the Department of Medical Research, Kaohsiung Medical University Hospital, Taiwan (KMU-TC108A03-11 and KMU-TC108A03-4, KMU-TC111A03-3) awarded to Fang-Rong Chang. We are also thankful for the instrumental support provided by the Center for Research Resources and Development (CRRD) at Kaohsiung Medical University and National Sun Yat-Sen University.