Codonopsinine derivatives as potential inhibitory agents against methicillin- resistant staphylococcus aureus (MRSA) / Saiful Azmi Johari

Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomialrelated and economically-relevant Gram-positive bacterial pathogen that has been known to display multidrug-resistance properties towards a wide range of structurally-unrelated antibiotics and antimicrobial agents. On the other hand,...

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Main Author:	Johari, Saiful Azmi
Format:	Book Section
Language:	English
Published:	Institute of Graduate Studies, UiTM 2018
Subjects:	Cultures and culture media. Culture technique. RS Pharmacy and materia medica
Online Access:	http://ir.uitm.edu.my/id/eprint/20701/ http://ir.uitm.edu.my/id/eprint/20701/1/ABS_SAIFUL%20AZMI%20JOHARI%20TDRA%20VOL%2013%20IGS_18.pdf

id	uitm-20701
recordtype	eprints
spelling	uitm-207012018-07-20T03:41:44Z http://ir.uitm.edu.my/id/eprint/20701/ Codonopsinine derivatives as potential inhibitory agents against methicillin- resistant staphylococcus aureus (MRSA) / Saiful Azmi Johari Johari, Saiful Azmi Cultures and culture media. Culture technique. RS Pharmacy and materia medica Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomialrelated and economically-relevant Gram-positive bacterial pathogen that has been known to display multidrug-resistance properties towards a wide range of structurally-unrelated antibiotics and antimicrobial agents. On the other hand, codonopsinine is a plant-based pyrrolidine alkaloid which is known to display remarkable antibiotic, hypotensive and low cytotoxic activity. Previously, 30 codonopsinine derivatives with electron rich functional groups were synthetically produced. In this study, selected microbiological and pre-clinical assays were carried out to investigate the possibility of using codonopsinine derivatives as potential new inhibitory agents against MRSA and methicillin-sensitive S. aureus (MSSA) isolates. In the MIC assay, only two novel compounds, MFM501 and MFM514, showed good inhibitory activity with MIC values between 7.81 to 31.3 μg/ml against 38 MRSA and 13 MSSA isolates. The MBC/MIC ratio exhibited that both active compounds has a bacteriostatic effect against MRSA and MSSA isolates. In the timekill studies, MFM501 showed a time-dependent killing action while MFM514 displayed a concentration-dependent killing effect. MFM514 also exhibited a faster bacteriostatic action than MFM501. Additionally, SEM analysis suggests that both active derivatives may exert its inhibitory activity via bacterial lysis and/or cytoplasmic membrane disruptions which resulted in the various irregular, distorted, shrunken and larger shapes of the treated MRSA cells. In the in vitro cytotoxic assay, both active molecules showed low cytotoxic activity with IC50 value of > 625 μg/ml against three non-cancerous mammalian cells. Following that, oral acute toxicity study revealed that the estimated LD50 value for MFM501 was > 300 mg/kg and < 2000 mg/kg (Category 4) while MFM514 exhibited less toxicity with an estimated LD50 value of > 2000 mg/kg and < 5000 mg/kg (Category 5). Finally, in the mouse protection assay, the ED50 values for MFM501 and MFM514 were calculated at 87.16 mg/kg and 29.39 mg/kg dosage, respectively, while both active codonopsinine derivatives exhibited a dose-dependent mice protection trend. This study showed that both active pyrrolidone compounds have the potential to be developed further as clinically active, safe and efficacious anti-MRSA agents. Since the dire need for new antibacterial agents are literally crucial for the survival of mankind, it is hoped that this study will serve as a proof-of concept paper to interested investors and/or healthcare-related companies for further R&D endeavour and/or commercial applications. Institute of Graduate Studies, UiTM 2018 Book Section PeerReviewed text en http://ir.uitm.edu.my/id/eprint/20701/1/ABS_SAIFUL%20AZMI%20JOHARI%20TDRA%20VOL%2013%20IGS_18.pdf Johari, Saiful Azmi (2018) Codonopsinine derivatives as potential inhibitory agents against methicillin- resistant staphylococcus aureus (MRSA) / Saiful Azmi Johari. In: The Doctoral Research Abstracts. IPSis Biannual Publication, 13 (13). Institute of Graduate Studies, UiTM, Shah Alam.
repository_type	Digital Repository
institution_category	Local University
institution	Universiti Teknologi MARA
building	UiTM Institutional Repository
collection	Online Access
language	English
topic	Cultures and culture media. Culture technique. RS Pharmacy and materia medica
spellingShingle	Cultures and culture media. Culture technique. RS Pharmacy and materia medica Johari, Saiful Azmi Codonopsinine derivatives as potential inhibitory agents against methicillin- resistant staphylococcus aureus (MRSA) / Saiful Azmi Johari
description	Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomialrelated and economically-relevant Gram-positive bacterial pathogen that has been known to display multidrug-resistance properties towards a wide range of structurally-unrelated antibiotics and antimicrobial agents. On the other hand, codonopsinine is a plant-based pyrrolidine alkaloid which is known to display remarkable antibiotic, hypotensive and low cytotoxic activity. Previously, 30 codonopsinine derivatives with electron rich functional groups were synthetically produced. In this study, selected microbiological and pre-clinical assays were carried out to investigate the possibility of using codonopsinine derivatives as potential new inhibitory agents against MRSA and methicillin-sensitive S. aureus (MSSA) isolates. In the MIC assay, only two novel compounds, MFM501 and MFM514, showed good inhibitory activity with MIC values between 7.81 to 31.3 μg/ml against 38 MRSA and 13 MSSA isolates. The MBC/MIC ratio exhibited that both active compounds has a bacteriostatic effect against MRSA and MSSA isolates. In the timekill studies, MFM501 showed a time-dependent killing action while MFM514 displayed a concentration-dependent killing effect. MFM514 also exhibited a faster bacteriostatic action than MFM501. Additionally, SEM analysis suggests that both active derivatives may exert its inhibitory activity via bacterial lysis and/or cytoplasmic membrane disruptions which resulted in the various irregular, distorted, shrunken and larger shapes of the treated MRSA cells. In the in vitro cytotoxic assay, both active molecules showed low cytotoxic activity with IC50 value of > 625 μg/ml against three non-cancerous mammalian cells. Following that, oral acute toxicity study revealed that the estimated LD50 value for MFM501 was > 300 mg/kg and < 2000 mg/kg (Category 4) while MFM514 exhibited less toxicity with an estimated LD50 value of > 2000 mg/kg and < 5000 mg/kg (Category 5). Finally, in the mouse protection assay, the ED50 values for MFM501 and MFM514 were calculated at 87.16 mg/kg and 29.39 mg/kg dosage, respectively, while both active codonopsinine derivatives exhibited a dose-dependent mice protection trend. This study showed that both active pyrrolidone compounds have the potential to be developed further as clinically active, safe and efficacious anti-MRSA agents. Since the dire need for new antibacterial agents are literally crucial for the survival of mankind, it is hoped that this study will serve as a proof-of concept paper to interested investors and/or healthcare-related companies for further R&D endeavour and/or commercial applications.
format	Book Section
author	Johari, Saiful Azmi
author_facet	Johari, Saiful Azmi
author_sort	Johari, Saiful Azmi
title	Codonopsinine derivatives as potential inhibitory agents against methicillin- resistant staphylococcus aureus (MRSA) / Saiful Azmi Johari
title_short	Codonopsinine derivatives as potential inhibitory agents against methicillin- resistant staphylococcus aureus (MRSA) / Saiful Azmi Johari
title_full	Codonopsinine derivatives as potential inhibitory agents against methicillin- resistant staphylococcus aureus (MRSA) / Saiful Azmi Johari
title_fullStr	Codonopsinine derivatives as potential inhibitory agents against methicillin- resistant staphylococcus aureus (MRSA) / Saiful Azmi Johari
title_full_unstemmed	Codonopsinine derivatives as potential inhibitory agents against methicillin- resistant staphylococcus aureus (MRSA) / Saiful Azmi Johari
title_sort	codonopsinine derivatives as potential inhibitory agents against methicillin- resistant staphylococcus aureus (mrsa) / saiful azmi johari
publisher	Institute of Graduate Studies, UiTM
publishDate	2018
url	http://ir.uitm.edu.my/id/eprint/20701/ http://ir.uitm.edu.my/id/eprint/20701/1/ABS_SAIFUL%20AZMI%20JOHARI%20TDRA%20VOL%2013%20IGS_18.pdf
first_indexed	2023-09-18T23:05:04Z
last_indexed	2023-09-18T23:05:04Z
_version_	1777418428359901184

Codonopsinine derivatives as potential inhibitory agents against methicillin- resistant staphylococcus aureus (MRSA) / Saiful Azmi Johari

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