Herbicidal Properties of Antihypertensive Drugs: Calcium Channel Blockers

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Abstract

Herbicide resistance is a worldwide problem in weed control. This prompts researchers to look for new modes of action to slow down the evolution of herbicide-resistant weeds. This research aims to determine the herbicidal action of thiazolo[3,2-a]pyrimidines derivatives, which are well known as antihypertensive drugs. The phytotoxic effects of ten compounds were investigated using leaf disc discoloration test and seed germination bioassay. At concentrations of 125 to 250 mg/L, the 5-(3-Fluoro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester ( c ) was highly active against Oldenlandia verticillata and Eleusine indica . At application rates of 1.25 to 2.5 kg ai/ha, formulated c demonstrated selective post-emergence and pre-emergence herbicidal activity against O. verticillata , E. indica and Cyperus iria . In the crop tolerance test, formulated c outperformed the commercial herbicide diuron, with aerobic Oryza sativa being the most tolerant, followed by Zea mays , and Brassica rapa . The addition of calcium chloride partially nullified compound c 's inhibitory effects on weed shoot growth, indicating that it has potential as a calcium channel blocker. Compound c acted by triggering electrolyte leakage without affecting photosystem II. These findings imply that c could be explored further as a template for developing new herbicides with novel modes of action.
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Herbicidal Properties of Antihypertensive Drugs: Calcium Channel Blockers | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Herbicidal Properties of Antihypertensive Drugs: Calcium Channel Blockers HANNAN SAFIYYAH TAN SIAN HUI Abdullah, Poh Wai Chia, Dzolkhifli Omar, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-436991/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Jul, 2021 Read the published version in Scientific Reports → Version 1 posted 9 You are reading this latest preprint version Abstract Herbicide resistance is a worldwide problem in weed control. This prompts researchers to look for new modes of action to slow down the evolution of herbicide-resistant weeds. This research aims to determine the herbicidal action of thiazolo[3,2-a]pyrimidines derivatives, which are well known as antihypertensive drugs. The phytotoxic effects of ten compounds were investigated using leaf disc discoloration test and seed germination bioassay. At concentrations of 125 to 250 mg/L, the 5-(3-Fluoro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester ( c ) was highly active against Oldenlandia verticillata and Eleusine indica . At application rates of 1.25 to 2.5 kg ai/ha, formulated c demonstrated selective post-emergence and pre-emergence herbicidal activity against O. verticillata , E. indica and Cyperus iria . In the crop tolerance test, formulated c outperformed the commercial herbicide diuron, with aerobic Oryza sativa being the most tolerant, followed by Zea mays , and Brassica rapa . The addition of calcium chloride partially nullified compound c 's inhibitory effects on weed shoot growth, indicating that it has potential as a calcium channel blocker. Compound c acted by triggering electrolyte leakage without affecting photosystem II. These findings imply that c could be explored further as a template for developing new herbicides with novel modes of action. Marine and Freshwater Biology Herbicide resistance Oldenlandia verticillata Zea mays herbicides Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Full-Text Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF. Additional Declarations No competing interests reported. Supplementary Files SupplementaryInformation.docx Cite Share Download PDF Status: Published Journal Publication published 09 Jul, 2021 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Major revision 17 Jun, 2021 Reviews received at journal 09 Jun, 2021 Reviewers agreed at journal 03 Jun, 2021 Reviewers agreed at journal 03 Jun, 2021 Reviewers invited by journal 03 Jun, 2021 Editor assigned by journal 03 Jun, 2021 Editor invited by journal 27 Apr, 2021 Submission checks completed at journal 27 Apr, 2021 First submitted to journal 18 Apr, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-436991","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":23486158,"identity":"1b8f8a54-3df7-429a-9643-c12029bdad95","order_by":0,"name":"HANNAN SAFIYYAH TAN SIAN HUI Abdullah","email":"","orcid":"","institution":"Universiti Malaysia Terengganu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"HANNAN","middleName":"SAFIYYAH TAN SIAN HUI","lastName":"Abdullah","suffix":""},{"id":23486159,"identity":"3a9db79c-dadb-4abc-ad56-5dd7064b5aea","order_by":1,"name":"Poh Wai Chia","email":"","orcid":"","institution":"Universiti Malaysia Terengganu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Poh","middleName":"Wai","lastName":"Chia","suffix":""},{"id":23486160,"identity":"772ba2cd-a2d7-4188-aaaf-5a77abfe98b0","order_by":2,"name":"Dzolkhifli Omar","email":"","orcid":"","institution":"Universiti Putra Malaysia","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dzolkhifli","middleName":"","lastName":"Omar","suffix":""},{"id":23486161,"identity":"83cc08dc-74fc-42d9-bdd6-345987ee9f38","order_by":3,"name":"Tse Seng Chuah","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYDACCQYGZiAlByYZoCQRWhIYjBmYmUnUktjAQKwW/tk9hp8Lf9SlbzjOf3QDQ4V1YoPYGQP8ltw5Yyw9I+Fw7obDzGw3GM6kJzZI5+DXYiCRYyDNk3AAooWx7TBRWox/8yTUpRuAtfwjTosZ0BbmBIiWBiK0SNxIK7PmSTtsOPMws9mNhGPpxm3SaQV4tfDPSN58m8emTp7v/MFnNz7UWMv2SydvwKsFFSQAMRsDB36HYQPsD0jWMgpGwSgYBcMaAAAIGUGauQQAZgAAAABJRU5ErkJggg==","orcid":"","institution":"Universiti Teknologi Mara","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Tse","middleName":"Seng","lastName":"Chuah","suffix":""}],"badges":[],"createdAt":"2021-04-18 11:14:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-436991/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-436991/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-021-93662-2","type":"published","date":"2021-07-09T15:00:49+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":8641184,"identity":"1709d839-855b-42df-8369-4a170db9919a","added_by":"auto","created_at":"2021-04-30 14:59:59","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":45153,"visible":true,"origin":"","legend":"Phytotoxic effect of thiazolo[3,2-a]pyrimidine carboxylate derivatives at 500 mg/L on green pigment degradation of Oldenlandia verticillata throughout seven days of incubation period. Each score representing different colour retention of leaf disc. Score 1: Green – The leaf disc surface is completely green; Score 2: Green brownish – 10-30% of leaf disc surface is dark brown in colour; Score 3: Brown greenish – 50-80% of leaf disc surface is dark brown in colour; Score 4: Dark brown – More than 90% of leaf disc surface, in aggregate, is dark brown. a: 7-Methyl-5-phenyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester; b: 5-(4-Fluoro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester; c: 5-(3-Fluoro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester; d: 5-(2-Fluoro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester; e: 5-(4-Chloro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester; f: 5-(3-Chloro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester; g: 5-(2-Chloro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester; h: 5-(4-Bromo-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester; i: 5-(3-Bromo-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester; j: 5-(2-Bromo-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester.","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-436991/v1/641fff8db4f37e28460ad136.jpg"},{"id":8641178,"identity":"6d983afc-2ed8-46e4-8bde-6e2fe1d1e68f","added_by":"auto","created_at":"2021-04-30 14:59:59","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":34652,"visible":true,"origin":"","legend":"Phytotoxic effects of 5-(3-Fluoro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester (c) at 0, 62.5,125, 250 and 500 mg/L on green pigment degradation of Oldenlandia verticillata throughout 10 days of incubation period. Each score representing different colour retention of leaf disc. Score 1: Green – The leaf disc surface is completely green; Score 2: Green brownish – 10-30% of leaf disc surface is dark brown in colour; Score 3: Brown greenish – 50-80% of leaf disc surface is dark brown in colour; Score 4: Dark brown – More than 90% of the leaf disc surface, in aggregate, is dark brown.","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-436991/v1/f4e7f4613bf089d230a4db07.jpg"},{"id":8641181,"identity":"abd196ba-80aa-49ff-90a1-6cf321de067c","added_by":"auto","created_at":"2021-04-30 14:59:59","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":36577,"visible":true,"origin":"","legend":"Inhibitory effect of 5-(3-Fluoro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester (c) on germination (A), shoot length (B) and root length (C) of Eleusine indica after 7 days of treatment. The standard deviation of the mean is symbolized by the vertical bar. 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5","display":"","copyAsset":false,"role":"figure","size":48607,"visible":true,"origin":"","legend":"Phytotoxic effects of c (−) and diuron (--) treatments on shoot dry weight of Brassica rapa (A), Zea mays (B) and Oryza sativa (C) respectively 3 weeks after post-emergence application.","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-436991/v1/0028440f57adc527740ad1ef.jpg"},{"id":8642073,"identity":"68e9d094-b9f7-4f6a-9b51-159f8ceddfd9","added_by":"auto","created_at":"2021-04-30 15:06:00","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":53776,"visible":true,"origin":"","legend":"Herbicidal effects of c (−) and diuron (--) treatments on shoot dry weight of Eleusine indica (A), Oldenlandia verticillata (B), and Cyperus iria (C) respectively 2 weeks after pre-emergence 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8","display":"","copyAsset":false,"role":"figure","size":53874,"visible":true,"origin":"","legend":"Herbicidal effects of c (−) and diuron (--) treatments on root length of Eleusine indica (A), Oldenlandia verticillata (B), and Cyperus iria (C) respectively 2 weeks after pre-emergence application.","description":"","filename":"8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-436991/v1/451e01c91dfdbc304e7f2588.jpg"},{"id":8641187,"identity":"5e832b9b-4b0e-4288-9be8-33c491fa16b8","added_by":"auto","created_at":"2021-04-30 15:00:00","extension":"jpg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":52038,"visible":true,"origin":"","legend":"Phytotoxic effects of c (−) and diuron (--) treatment on shoot dry weight of Brassica rapa (A), Oryza sativa (B) and Zea mays (C) 2 weeks after pre-emergence 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