TY - JOUR
T1 - Nornidulin, A New Inhibitor of Plasmodium falciparum Malate
T2 - Quinone Oxidoreductase (PfMQO) from Indonesian Aspergillus sp. BioMCC f.T.8501
AU - Cahyono, Alfian Wika
AU - Fitri, Loeki Enggar
AU - Winarsih, Sri
AU - Prabandari, Erwahyuni Endang
AU - Waluyo, Danang
AU - Pramisandi, Amila
AU - Chrisnayanti, Evita
AU - Dewi, Diana
AU - Siska, Eka
AU - Nurlaila, Nurlaila
AU - Nugroho, Nuki Bambang
AU - Nozaki, Tomoyoshi
AU - Suciati, Suciati
N1 - Funding Information:
The authors would like to thank to The Ministry of Education, Culture, Research, and Technology of the Republic of Indonesia and the Faculty of Medicine, Universitas Brawijaya for providing the research grant. We also thank the Laboratory for Biotechnology, National Research and Innovation Agency (BRIN), BJ Habibie Science and Technology Park, South Tangerang-Banten, Indonesia for their research facilities.
Funding Information:
This work was partly funded by a grant from the Program Magister Menuju Doktor Sarjana Unggul from The Ministry of Education, Culture, Research, and Technology of 2021 to Brawijaya University, Doctoral and Professor Research Grants from the Faculty of Medicine of Universitas Brawijaya of 2022, and a grant from the Science and Technology Research Partnership for Sustainable Development (SATREPS) from the Japan Agency for Medical Research and Development (AMED) to the University of Tokyo and from Japan International Cooperation Agency (JICA) to the National Research and Innovation Agency (BRIN).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/2
Y1 - 2023/2
N2 - This study aimed to obtain a microbial active compound as a novel antimalarial drug from Indonesian isolates. Target-based assays were used to screen for antimalarial activity against the parasite mitochondrial, Plasmodium falciparum malate:quinone oxidoreductase (PfMQO) enzyme. In total, 1600 crude extracts, composed from 800 fungi and 800 actinomycetes extracts, were screened against PfMQO, yielding six active extracts as primary hits. After several stages of stability tests, one extract produced by Aspergillus sp. BioMCC f.T.8501 demonstrated stable PfMQO inhibitory activity. Several purification stages, including OCC, TLC, and HPLC, were performed to obtain bioactive compounds from this active extract. All purification steps were followed by an assay against PfMQO. We identified the active compound as nornidulin based on its LC-MS and UV spectrum data. Nornidulin inhibited PfMQO activity at IC50 of 51 µM and P. falciparum 3D7 proliferation in vitro at IC50 of 44.6 µM, however, it had no effect on the growth of several mammalian cells. In conclusion, we isolated nornidulin from Indonesian Aspergillus sp. BioMCC f.T.8501 as a novel inhibitor of PfMQO, which showed inhibitory activity against the proliferation of P. falciparum 3D7 in vitro.
AB - This study aimed to obtain a microbial active compound as a novel antimalarial drug from Indonesian isolates. Target-based assays were used to screen for antimalarial activity against the parasite mitochondrial, Plasmodium falciparum malate:quinone oxidoreductase (PfMQO) enzyme. In total, 1600 crude extracts, composed from 800 fungi and 800 actinomycetes extracts, were screened against PfMQO, yielding six active extracts as primary hits. After several stages of stability tests, one extract produced by Aspergillus sp. BioMCC f.T.8501 demonstrated stable PfMQO inhibitory activity. Several purification stages, including OCC, TLC, and HPLC, were performed to obtain bioactive compounds from this active extract. All purification steps were followed by an assay against PfMQO. We identified the active compound as nornidulin based on its LC-MS and UV spectrum data. Nornidulin inhibited PfMQO activity at IC50 of 51 µM and P. falciparum 3D7 proliferation in vitro at IC50 of 44.6 µM, however, it had no effect on the growth of several mammalian cells. In conclusion, we isolated nornidulin from Indonesian Aspergillus sp. BioMCC f.T.8501 as a novel inhibitor of PfMQO, which showed inhibitory activity against the proliferation of P. falciparum 3D7 in vitro.
KW - Aspergillus sp. BioMCC f.T.8501
KW - PfMQO
KW - Plasmodium falciparum
KW - malaria
KW - nornidulin
KW - purification
UR - http://www.scopus.com/inward/record.url?scp=85149141190&partnerID=8YFLogxK
U2 - 10.3390/ph16020268
DO - 10.3390/ph16020268
M3 - Article
AN - SCOPUS:85149141190
SN - 1424-8247
VL - 16
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 2
M1 - 268
ER -
