{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:22:47Z","timestamp":1790205767644,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T00:00:00Z","timestamp":1552435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004530","name":"Universiti Putra Malaysia","doi-asserted-by":"publisher","award":["RUGS, Grant No. 04-02-1756 RU and GP\/2018\/9612800"],"award-info":[{"award-number":["RUGS, Grant No. 04-02-1756 RU and GP\/2018\/9612800"]}],"id":[{"id":"10.13039\/501100004530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004530","name":"Universiti Putra Malaysia","doi-asserted-by":"publisher","award":["RUGS, Grant No. 04-02-1756 RU and GP\/2018\/9612800"],"award-info":[{"award-number":["RUGS, Grant No. 04-02-1756 RU and GP\/2018\/9612800"]}],"id":[{"id":"10.13039\/501100004530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Antibiotic resistance is a problem that continues to challenge the healthcare sector, especially in clinically significant pathogens like methicillin-resistant Staphylococcus aureus (MRSA). Herein is described the isolation and structure elucidation of a bioactive compound from Allium stipitatum with antimicrobial activity. Crude Allium stipitatum dichloromethane extract (ASDE) was subjected to systematic purification by chromatographic procedures to afford various bioactive fractions. A fraction that exhibited anti-MRSA activity (4 \u00b5g\u00b7mL\u22121) was further characterized to determine the structure. The structure of the compound was elucidated as 2-(methyldithio)pyridine-3-carbonitrile (2-Medpy-3-CN). The 2-Medpy-3-CN compound, which was screened for antimicrobial activity, exhibited minimum inhibitory concentrations (MICs) in the range of 0.5 to &gt;64 \u00b5g\u00b7mL\u22121 for tested bacterial species and 0.25 to 2 \u00b5g\u00b7mL\u22121 for Candida spp. Further studies are important to confirm the drug target and mechanism of action.<\/jats:p>","DOI":"10.3390\/molecules24061003","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T04:15:29Z","timestamp":1552536929000},"page":"1003","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Bioactive 2-(Methyldithio)Pyridine-3-Carbonitrile from Persian Shallot (Allium stipitatum Regel.) Exerts Broad-Spectrum Antimicrobial Activity"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-8931","authenticated-orcid":false,"given":"Arunkumar","family":"Karunanidhi","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor Darul Ehsan, Malaysia"},{"name":"Department of Pharmacology and Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, Bandar Puncak Alam 42300, Selangor Darul Ehsan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8484-7166","authenticated-orcid":false,"given":"Ehsanollah","family":"Ghaznavi-Rad","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Medicine, Arak University of Medical Sciences, Basij Square, Arak 38481-7-6941, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayakayatri","family":"Jeevajothi Nathan","sequence":"additional","affiliation":[{"name":"School of Medicine, Taylor\u2019s University, Lakeside Campus, No. 1, Jalan Taylor\u2019s, Subang Jaya 47500, Selangor Darul Ehsan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narcisse","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor Darul Ehsan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1081-2964","authenticated-orcid":false,"given":"Sridevi","family":"Chigurupati","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraidah 52571, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fazlin","family":"Mohd Fauzi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, Bandar Puncak Alam 42300, Selangor Darul Ehsan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mallikarjuna Rao","family":"Pichika","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126 Jalan Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6288-3791","authenticated-orcid":false,"given":"Rukman Awang","family":"Hamat","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor Darul Ehsan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie Than Thian","family":"Lung","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor Darul Ehsan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"van Belkum","sequence":"additional","affiliation":[{"name":"R &amp; D Microbiology, BioMerieux, 3 route de Port Michaud, 38390 La Balme-les-Grottes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasanthakumari","family":"Neela","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor Darul Ehsan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,13]]},"reference":[{"key":"ref_1","first-page":"273","article-title":"The escalating challenge of vancomycin resistance in Staphylococcus Aureus","volume":"4","author":"Pfeltz","year":"2004","journal-title":"Curr. Drug Targets"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/S1473-3099(01)00145-1","article-title":"Vancomycin-resistant enterococci: Why are they here, and where do they come from?","volume":"15","author":"Bonten","year":"2001","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/nrmicro1789","article-title":"An increasing threat in hospitals: Multidrug-resistant Acinetobacter Baumannii","volume":"5","author":"Dijkshoorn","year":"2007","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e603","DOI":"10.1016\/j.ijid.2012.04.004","article-title":"Stenotrophomonas maltophilia in Malaysia: Molecular epidemiology and trimethoprim-sulfamethoxazole resistance","volume":"16","author":"Neela","year":"2012","journal-title":"Int. J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1086\/599039","article-title":"Epidemiology and outcomes of candidemia in 2019 patients: Data from the prospective antifungal therapy alliance registry","volume":"48","author":"Horn","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ijantimicag.2011.02.016","article-title":"Candida bloodstream infections: Comparison of species distribution and resistance to echinocandin and azole antifungal agents in Intensive Care Unit (ICU) and non-ICU settings in the SENTRY Antimicrobial Surveillance Program (2008\u20132009)","volume":"38","author":"Pfaller","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1128\/CMR.05022-11","article-title":"Predictors of mortality in Staphylococcus aureus Bacteremia","volume":"25","author":"Jensen","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1086\/502523","article-title":"Costs and outcomes among hemodialysis-dependent patients with methicillin-resistant or methicillin-susceptible Staphylococcus aureus bacteremia","volume":"26","author":"Reed","year":"2005","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1086\/502417","article-title":"Risk factors and costs associated with methicillin-resistant Staphylococcus aureus bloodstream infections","volume":"25","author":"McHugh","year":"2004","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1086\/502522","article-title":"The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: Mortality, length of stay, and hospital charges","volume":"26","author":"Cosgrove","year":"2005","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.tips.2016.05.001","article-title":"Natural Products as a Source for Novel Antibiotics","volume":"37","author":"Moloney","year":"2016","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1021\/acs.jnatprod.5b01055","article-title":"Natural Products as Sources of New Drugs from 1981 to 2014","volume":"79","author":"Newman","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.4103\/phrev.phrev_21_17","article-title":"Developing New Antimicrobial Therapies: Are Synergistic Combinations of Plant Extracts\/Compounds with Conventional Antibiotics the Solution?","volume":"11","author":"Cheesman","year":"2017","journal-title":"Pharmacogn. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jaim.2017.05.004","article-title":"Development of botanicals to combat antibiotic resistance","volume":"8","author":"Gupta","year":"2017","journal-title":"J. Ayurveda Integr. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"106","DOI":"10.4103\/0973-7847.65321","article-title":"Extracts from the history and medical properties of garlic","volume":"4","author":"Petrovska","year":"2010","journal-title":"Pharmacogn. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1106S","DOI":"10.1093\/jn\/131.3.1106S","article-title":"Protection against Helicobacter pylori and other bacterial infections by garlic","volume":"131","author":"Sivam","year":"2001","journal-title":"J. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e14814","DOI":"10.5812\/jjm.14814","article-title":"Fresh Garlic Extract Enhances the Antimicrobial Activities of Antibiotics on Resistant Strains in Vitro","volume":"8","author":"Li","year":"2015","journal-title":"Jundishapur J. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12","DOI":"10.4103\/0976-9668.71666","article-title":"Antibacterial activity of garlic extract on streptomycin-resistant Staphylococcus aureus and Escherichia coli solely and in synergism with streptomycin","volume":"1","author":"Palaksha","year":"2010","journal-title":"J. Nat. Sci. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Reiter, J., Levina, N., van der Linden, M., Gruhlke, M., Martin, C., and Slusarenko, A.J. (2017). Diallylthiosulfinate (Allicin), a Volatile Antimicrobial from Garlic (Allium sativum), Kills Human Lung Pathogenic Bacteria, Including MDR Strains, as a Vapor. Molecules, 22.","DOI":"10.3390\/molecules22101711"},{"key":"ref_20","first-page":"1","article-title":"Genetic diversity of persian shallot (Allium hirtifolium) ecotypes based on morphological traits, allicin content and RAPD markers","volume":"1","author":"Asili","year":"2010","journal-title":"Open Access J. Med. Aromat. Plants"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.scienta.2008.08.032","article-title":"Genetic diversity evaluation of wild Persian shallot (Allium hirtifolium Boiss.) using morphological and RAPD markers","volume":"119","author":"Ebrahimi","year":"2009","journal-title":"Sci. Hortic."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1914732","DOI":"10.1155\/2017\/1914732","article-title":"Allium stipitatum extract exhibits in vivo antibacterial activity against methicillin-resistant Staphylococcus aureus and accelerates burn wound healing in a full-thickness murine burn model","volume":"2017","author":"Karunanidhi","year":"2017","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9845075","DOI":"10.1155\/2018\/9845075","article-title":"Antibacterial and Antibiofilm Activities of Nonpolar Extracts of Allium stipitatum Regel. against Multidrug Resistant Bacteria","volume":"2018","author":"Karunanidhi","year":"2018","journal-title":"Biomed Res. Int."},{"key":"ref_24","first-page":"1","article-title":"Antifungal and antibiofilm activity of Persian shallot (Allium stipitatum Regel.) against clinically significant Candida spp.","volume":"35","author":"Karunanidhi","year":"2018","journal-title":"Trop. Biomed."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1038\/s41598-017-18948-w","article-title":"Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition","volume":"8","author":"Danquah","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1021\/np800572r","article-title":"Bioactive pyridine-N-oxide disulfides from Allium stipitatum","volume":"72","author":"Poeschl","year":"2009","journal-title":"J. Nat. Prod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/S0031-9422(02)00335-7","article-title":"Insecticidal sesquiterpene pyridine alkaloids from Euonymus species","volume":"61","author":"Jinbo","year":"2002","journal-title":"Phytochemistry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.jep.2014.03.066","article-title":"Antiinflammatory and neurological activity of pyrithione and related sulfur-containing pyridine N-oxides from Persian shallot (Allium stipitatum)","volume":"154","author":"Stafford","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S0003-2697(02)00010-6","article-title":"A spectrophotometric assay for allicin, alliin, and alliinase (Alliin lyase) with a chromogenic thiol: Reaction of 4-mercaptopyridine with thiosulfinates","volume":"307","author":"Miron","year":"2002","journal-title":"Anal. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.jiac.2017.04.012","article-title":"New 1-hydroxy-2-thiopyridine derivatives active against both replicating and dormant Mycobacterium tuberculosis","volume":"23","author":"Salina","year":"2017","journal-title":"J. Infect. Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1128\/AAC.01308-13","article-title":"New 2-thiopyridines as potential candidates for killing both actively growing and dormant Mycobacterium tuberculosis cells","volume":"58","author":"Salina","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_32","first-page":"667","article-title":"A concise synthesis and antimicrobial activity of a novel series of naphthylpyridine-3-carbonitrile compounds","volume":"70","author":"Kotb","year":"2013","journal-title":"Acta Pol. Pharm."},{"key":"ref_33","first-page":"1077","article-title":"Anti-inflammatory and antimicrobial activity of 4,5-dihydropyrimidine-5-carbonitrile derivatives: Their synthesis and spectral elucidation","volume":"69","author":"Alam","year":"2012","journal-title":"Acta Pol. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"479","DOI":"10.2478\/v10007-010-0033-8","article-title":"Antimicrobial activity of some synthesized glucopyranosyl-pyrimidine carbonitrile and fused pyrimidine systems","volume":"60","author":"Sayed","year":"2010","journal-title":"Acta Pharm."},{"key":"ref_35","first-page":"31","article-title":"Pyrimidine-5-carbonitriles II: Synthesis and antimicrobial activity of novel 6-alkyl-2,4-disubstituted pyrimidine-5-carbonitriles","volume":"64","author":"Habib","year":"2014","journal-title":"Drug Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Schwalbe, R., Steele-Moore, L., and Goodwin, A.C. (2007). Macro- and microdilution methods of antimicrobial susceptibility testing. Antimicrobial Susceptibility Testing Protocols, CRC Press Taylor & Francis Group.","DOI":"10.1201\/9781420014495"},{"key":"ref_37","unstructured":"(2012). Performance Standards for Antimicrobial Susceptibility Testing, Clinical Laboratory Standards Institutes. Twenty-Second Informational Supplement."},{"key":"ref_38","unstructured":"(2015). Performance Standards for Antimicrobial Susceptibility Testing, Clinical Laboratory Standards Institutes. Twenty-Fifth Informational Supplement."},{"key":"ref_39","unstructured":"Schr\u00f6dinger (2013). QikProp, Schr\u00f6dinger LLC. version 3.4."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/6\/1003\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:38:23Z","timestamp":1760186303000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/6\/1003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,13]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["molecules24061003"],"URL":"https:\/\/doi.org\/10.3390\/molecules24061003","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,13]]}}}