Isolation and Characterization of Werneria Chromene and Dihydroxyacidissimol from <i>Burkillanthus</i> <i>malaccensis</i> (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
Affiliations
Masyitah Zulkipli
School of Pharmacy, University of Nottingham Malaysia Campus, Semenyih 43500, Malaysia
Nuzum Mahbub
School of Pharmacy, University of Nottingham Malaysia Campus, Semenyih 43500, Malaysia
Ayesha Fatima
Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul 34093, Turkey
Stefanie Lim Wan-Lin
School of Pharmacy, University of Nottingham Malaysia Campus, Semenyih 43500, Malaysia
Teng-Jin Khoo
School of Pharmacy, University of Nottingham Malaysia Campus, Semenyih 43500, Malaysia
Tooba Mahboob
Department of Medical Microbiology, University of Malaya, Kuala Lumpur 50603, Malaysia
Mogana Rajagopal
Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
Chandramathi Samudi
Department of Medical Microbiology, University of Malaya, Kuala Lumpur 50603, Malaysia
Gheetanjali Kathirvalu
Department of Medical Microbiology, University of Malaya, Kuala Lumpur 50603, Malaysia
Nor Hayati Abdullah
Natural Product Division, Forest Research Institute Malaysia (FRIM), Kepong 52109, Malaysia
Ana Rita Pinho
Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal
Sonia M. R. Oliveira
CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal
Maria de Lourdes Pereira
Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal
Mohammed Rahmatullah
Department of Biotechnology & Genetic Engineering, University of Development Alternative, Lalmatia, Dhaka 1207, Bangladesh
Anamul Hasan
Department of Biotechnology & Genetic Engineering, University of Development Alternative, Lalmatia, Dhaka 1207, Bangladesh
Alok K. Paul
School of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS 7001, Australia
Mark S. Butler
Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia
Muhammad Nawaz
Department of Nano-Medicine, Institute for Research and Medical Consultations (IRM), Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia
Polrat Wilairatana
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
Veeranoot Nissapatorn
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
Christophe Wiart
Institute for Tropical Biology and Conservation, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu 88400, Malaysia
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.
