Isolation and Characterization of Werneria Chromene and Dihydroxyacidissimol from Burkillanthus malaccensis (Ridl.) Swingle

Masyitah Zulkipli; Nuzum Mahbub; Ayesha Fatima; Stefanie Lim Wan-Lin; Teng-Jin Khoo; Tooba Mahboob; Mogana Rajagopal; Chandramathi Samudi; Gheetanjali Kathirvalu; Nor Hayati Abdullah; Ana Rita Pinho; Sonia M R Oliveira; Maria de Lourdes Pereira; Mohammed Rahmatullah; Anamul Hasan; Alok K Paul; Mark S Butler; Muhammad Nawaz; Polrat Wilairatana; Veeranoot Nissapatorn; Christophe Wiart

doi:10.3390/plants11111388

Isolation and Characterization of Werneria Chromene and Dihydroxyacidissimol from Burkillanthus malaccensis (Ridl.) Swingle

Plants (Basel). 2022 May 24;11(11):1388. doi: 10.3390/plants11111388.

Authors

Masyitah Zulkipli¹, Nuzum Mahbub¹, Ayesha Fatima², Stefanie Lim Wan-Lin¹, Teng-Jin Khoo¹, Tooba Mahboob³, Mogana Rajagopal⁴, Chandramathi Samudi³, Gheetanjali Kathirvalu³, Nor Hayati Abdullah⁵, Ana Rita Pinho^{6

7}, Sonia M R Oliveira^{8

9}, Maria de Lourdes Pereira^{6

8}, Mohammed Rahmatullah¹⁰, Anamul Hasan¹⁰, Alok K Paul¹¹, Mark S Butler¹², Muhammad Nawaz¹³, Polrat Wilairatana¹⁴, Veeranoot Nissapatorn¹⁵, Christophe Wiart¹⁶

Affiliations

¹ School of Pharmacy, University of Nottingham Malaysia Campus, Semenyih 43500, Malaysia.
² Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul 34093, Turkey.
³ Department of Medical Microbiology, University of Malaya, Kuala Lumpur 50603, Malaysia.
⁴ Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia.
⁵ Natural Product Division, Forest Research Institute Malaysia (FRIM), Kepong 52109, Malaysia.
⁶ Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal.
⁷ Neuroscience and Signaling Laboratory, Institute of Biomedicine-IBIMED, University of Aveiro, 3810-193 Aveiro, Portugal.
⁸ CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal.
⁹ Hunter Medical Research Institute (HMRI), New Lambton Heights, NSW 2305, Australia.
¹⁰ Department of Biotechnology & Genetic Engineering, University of Development Alternative, Lalmatia, Dhaka 1207, Bangladesh.
¹¹ School of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS 7001, Australia.
¹² Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia.
¹³ Department of Nano-Medicine, Institute for Research and Medical Consultations (IRM), Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia.
¹⁴ Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
¹⁵ School of Allied Health Sciences, World Union for Herbal Drug Discovery (WUHeDD), Research Excellence Center for Innovation and Health Products (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand.
¹⁶ Institute for Tropical Biology and Conservation, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu 88400, Malaysia.

Abstract

The secondary metabolites of endemic plants from the Rutaceae family, such as Burkillanthusmalaccensis (Ridl.) Swingle from the rainforest of Malaysia, has not been studied. Burkillanthusmalaccensis (Ridl.) Swingle may produce antibacterial and antibiotic-potentiating secondary metabolites. Hexane, chloroform, and methanol extracts of leaves, bark, wood, pericarps, and endocarps were tested against bacteria by broth microdilution assay and their antibiotic-potentiating activities. Chromatographic separations of hexane extracts of seeds were conducted to investigate effective phytochemicals and their antibacterial activities. Molecular docking studies of werneria chromene and dihydroxyacidissiminol against SARS-CoV-2 virus infection were conducted using AutoDock Vina. The methanol extract of bark inhibited the growth of Staphylococcusaureus, Escherichiacoli, and Pseudomonasaeruginosa with the minimum inhibitory concentration of 250, 500, and 250 µg/mL, respectively. The chloroform extract of endocarps potentiated the activity of imipenem against imipenem-resistant Acinetobacterbaumannii. The hexane extract of seeds increased the sensitivity of P. aeruginosa against ciprofloxacin and levofloxacin. The hexane extract of seeds and chloroform extract of endocarps were chromatographed, yielding werneria chromene and dihydroxyacidissiminol. Werneria chromene was bacteriostatic for P.aeruginosa and P.putida, with MIC/MBC values of 1000 > 1000 µg/mL. Dihydroxyacidissiminol showed the predicted binding energies of −8.1, −7.6, −7.0, and −7.5 kcal/mol with cathepsin L, nsp13 helicase, SARS-CoV-2 main protease, and SARS-CoV-2 spike protein receptor-binding domain S-RBD. Burkillanthusmalaccensis (Ridl.) Swingle can be a potential source of natural products with antibiotic-potentiating activity and that are anti-SARS-CoV-2.

Keywords: Burkillanthus malaccensis; SARS-CoV-2; antibiotic potentiator; cathepsin L; dihydroxyacidissiminol; nsp13 helicase; spike protein; werneria chromene.

Grants and funding

This project was funded by a grant from the Malaysian Ministry of Education (FRGS/1/2018/WAB07/UNIM/02/1, Malaysian Ministry of Higher Education, Malaysia). Project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020, financed by national funds through the FCT/MEC (PIDDAC) is acknowledged. We also would like to acknowledge the project entitled “Medicinal plants as anti-viral activity against important emerging viruses” The Plant Genetics Conservation Project under the Royal Initiation of Her Royal Highness Princess Maha Chakri Sirindhorn, Walailak University, Thailand (Grant No. 032-2565). Dr. Muhammad Nawaz is thankful to the Deanship of Scientific Research (DSR) at Imam Abdulrahman Bin Faisal University (IAU) for financial support through project no. COVID-19-2020-003-IRMC. In addition, we would like to thank Mr. Hassan and Mr. Pidji for guiding us in the rainforest of Perak.