GSK-3β inhibition with antiplasmodial activities from the extracts of actinomycetes isolated from Malaysian forest soil

Fauze Mahmud; Amatul Hamizah Ali; Dg Nur Azierah Fachyuni Abdul Aziz; Salahaudin Maili; Mary Jembun; Suhaini Sudi; Noor Dhiana Efani Dahari; Ngit Shin Lai; Siew Eng How; Jualang Azlan Gansau; Hasidah Mohd Sidek; Noor Embi; Ping-chin Lee

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GSK-3β inhibition with antiplasmodial activities from the extracts of actinomycetes isolated from Malaysian forest soil

Author: Fauze Mahmud ^{1
,

2
,

3} ; Amatul Hamizah Ali ⁴ ; Dg Nur Azierah Fachyuni Abdul Aziz ¹ ; Salahaudin Maili ¹ ; Mary Jembun ¹ ; Suhaini Sudi ^{1
,

3} ; Noor Dhiana Efani Dahari ⁴ ; Ngit Shin Lai ² ; Siew Eng How ¹ ; Jualang Azlan Gansau ^{1
,

3} ; Hasidah Mohd Sidek ⁴ ; Noor Embi ⁴ ; Ping-Chin Lee ^{1
,

3
,

5}
Author Information

1. Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia.&
2. Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 USM, Pulau Pinang, Malaysia.&
3. BioAgriTech (BioATR) Research Group, Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia.&
4. Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM, Bangi, Selangor, Malaysia.
5. Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia.
Publication Type:Journal Article
Keywords: Anti-plasmodial activities; GSK-3β inhibitors; soil actinomycetes
From:Malaysian Journal of Microbiology 2023;19(no.6):664-670
CountryMalaysia
Language:English
Abstract: Aims:Glycogen synthase kinase-3 (GSK-3 (EC:2.7.11.1)) is one of the main therapeutic targets for treating cancer, diabetes, neurological illness and parasitic infection. Due to their distinctive structural characteristics and wide-ranging biological actions, small compounds from soil bacteria have been the most sought-after source for GSK-3 inhibitors. This study assessed the activities of soil actinomycetes isolated from Sabah, Malaysia, against human GSK-3β.
Methodology and results:A total of 514 actinomycetes strains were isolated from 144 soil samples. The activities of the crude extracts were evaluated against GSK-3β and its upstream regulators (MKK1 and PP1/GLC7) using yeast-based assays. Eight actinomycetes extracts showed selective human GSK-3β inhibition without affecting MKK1 and PP1/GLC7. The extract from one of these eight isolates, FA013, also showed potent and selective anti-plasmodial activities against Plasmodium falciparum 3D7 strain (IC50 = 0.18 μg/mL, SI = 13,850) with a non-toxic effect against Chang liver cells.
Conclusion, significance and impact of study :This study identified FA013 as a potential isolate from Malaysian rainforest soil with inhibitory activities against GSK-3β and malaria parasites for future drug development.
Full text:20.2023my0070.pdf