{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T10:56:34Z","timestamp":1784199394936,"version":"3.55.0"},"reference-count":24,"publisher":"FapUNIFESP (SciELO)","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Braz. J. Biol."],"abstract":"<jats:p>Abstract  Introduction Since antiquity, natural products have been widely used to relieve symptoms and prevent numerous diseases. Early treatments for vascular disorders, including thrombosis, relied heavily on plant-derived substances, which later served as prototypes for the development of platelet aggregation inhibitors and coagulation-modulating agents. Among these bioactive constituents, phenolic compounds\u2014abundantly found in various botanical sources\u2014have gained prominence due to their well-established antioxidant properties and reported anticoagulant effects. Recent studies highlight that the structural diversity of phenolic acids, particularly cinnamic acid (CA) and its derivatives, offers a valuable chemical scaffold for developing new therapeutic agents targeting thrombogenesis and oxidative imbalance.  Objective This study aimed to evaluate, in vitro, the pharmacological (anticoagulant and antioxidant) and toxicological (oxidant and cytotoxic) activities of cinnamic acid (CA) and five synthetic derivatives\u20144HDCN, 4MTCN, 3,4DHCN, 3,4DMCN, and 3H4MCN.  Methods Anticoagulant activity was assessed using a semi-automated coagulometer by measuring clotting time after exposure of human plasma to each molecule. Antioxidant, oxidant, and cytotoxic (hemolytic) activities were determined using human erythrocytes from blood groups A, B, and O. Oxidative and antioxidant responses were quantified by spectrophotometry following exposure to phenylhydrazine as a pro-oxidant inducer. Hemolysis was evaluated at concentrations ranging from 0 to 400 mg\/dL.  Results In the anticoagulant assays, the derivative 3,4DHCN exhibited the strongest activity, prolonging clotting time to 176.6 s, slightly surpassing 3,4MTCN (165.6 s). All molecules demonstrated low or negligible oxidizing activity (&lt;7.1%). Regarding antioxidant potential, 4MTCN showed the most effective protection against phenylhydrazine-induced oxidation, reducing oxidative damage to 8.7%. None of the tested compounds induced moderate or high hemolysis at concentrations up to 200 mg\/dL. However, at 400 mg\/dL, CA and 4HDCN produced high hemolytic rates across erythrocyte types. In type A cells, hemolysis reached 89.4% (CA) and 76.0% (4HDCN); in type B, 64.3% and 60.5%; and in type O, 90.1% and 70.7%, respectively.  Conclusion Dihydroxylated and dimethoxylated cinnamic acid derivatives demonstrated notable anticoagulant activity, minimal oxidative effects, low antioxidant capacity, and an absence of cytotoxicity in human erythrocytes at therapeutically relevant concentrations. These findings indicate that such molecules represent promising candidates for the development of new anticoagulant agents with favorable safety profiles.<\/jats:p>","DOI":"10.1590\/1519-6984.303373","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:32:23Z","timestamp":1780054343000},"source":"Crossref","is-referenced-by-count":1,"title":["Anticoagulant, antioxidant and cytotoxic potential of cinnamic acid and derivatives"],"prefix":"10.1590","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0575-0831","authenticated-orcid":false,"given":"P. E. A.","family":"Oliveira","sequence":"first","affiliation":[{"name":"Universidade Federal da Para\u00edba,  Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5403-0609","authenticated-orcid":false,"given":"D. P.","family":"Silva","sequence":"additional","affiliation":[{"name":"Universidade Federal da Para\u00edba,  Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3268-4270","authenticated-orcid":false,"given":"S. S.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universidade Federal da Para\u00edba,  Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5931-4686","authenticated-orcid":false,"given":"D. P.","family":"Marchi-Salvador","sequence":"additional","affiliation":[{"name":"Universidade Federal da Para\u00edba,  Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7466-9933","authenticated-orcid":false,"given":"A. A.","family":"Oliveira Filho","sequence":"additional","affiliation":[{"name":"Universidade Federal de Campina Grande,  Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"530","published-online":{"date-parts":[[2026]]},"reference":[{"issue":"5","key":"ref1","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1007\/s00044-013-0829-4","article-title":"Thrombin inhibitory activity of some polyphenolic compounds","volume":"23","author":"BIJAK M.","year":"2014","journal-title":"Medicinal Chemistry Research : An International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents"},{"key":"ref2","doi-asserted-by":"crossref","DOI":"10.26633\/RPSP.2020.1","article-title":"The adult mortality profile by cause of death in 10 Latin American countries (2000\u20132016)","volume":"44","author":"CALAZANS J.A.","year":"2020","journal-title":"Revista Panamericana de Salud P\u00fablica = Pan American Journal of Public Health"},{"issue":"1","key":"ref3","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1038\/s41598-020-59451-z","article-title":"Structure-antioxidant activity relationship of methoxy, phenolic hydroxyl, and carboxylic acid groups of phenolic acids","volume":"10","author":"CHEN J.","year":"2020","journal-title":"Scientific Reports"},{"issue":"2","key":"ref4","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/sj.bjp.0705776","article-title":"Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?","volume":"142","author":"HALLIWELL B.","year":"2004","journal-title":"British Journal of Pharmacology"},{"issue":"1","key":"ref5","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0925-4439(97)00013-6","article-title":"Structure and differential target sensitivity of the stimulable cytotoxic complex from hemolymph of the Mediterranean mussel Mytilus galloprovincialis. Biochimica et Biophysica Acta (BBA) -","volume":"1361","author":"HUBERT F.","year":"1997","journal-title":"Biochimica et Biophysica Acta"},{"issue":"1","key":"ref6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.29328\/journal.abb.1001030","article-title":"Effect of fresh red grape juice and grape fermentative product on oxidative-stress in human erythrocytes in vitro","volume":"6","author":"KESHAVARZI A.","year":"2022","journal-title":"Archives of Biotechnology and Biomedicine"},{"issue":"3","key":"ref7","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.3390\/molecules20033697","article-title":"Bioassay-guided fractionation of Melastoma malabathricum Linn. leaf solid phase extraction fraction and its anticoagulant activity","volume":"20","author":"KHOO L.","year":"2015","journal-title":"Molecules"},{"issue":"25","key":"ref8","doi-asserted-by":"crossref","first-page":"3929","DOI":"10.2174\/092986711803414395","article-title":"Coumarins as Antioxidants","volume":"18","author":"KOSTOVA I.","year":"2011","journal-title":"Current Medicinal Chemistry"},{"issue":"1","key":"ref9","doi-asserted-by":"crossref","first-page":"24","DOI":"10.5530\/fra.2014.1.5","article-title":"Assessment of the antioxidant and antiradicalic capacities in vitro of different phenolic derivatives","volume":"4","author":"KUCUKOGLU K.","year":"2014","journal-title":"Free Radicals and Antioxidants"},{"issue":"10","key":"ref10","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.3390\/life11101095","article-title":"Bioactive natural compounds with antiplatelet and anticoagulant activity and their potential role in the treatment of thrombotic disorders","volume":"11","author":"LAMPONI S.","year":"2021","journal-title":"Life"},{"issue":"3","key":"ref11","doi-asserted-by":"crossref","first-page":"11108","DOI":"10.34119\/bjhrv4n3-117","article-title":"Trombose Venosa Profunda: \u201cConhecer \u00e9 a melhor maneira de prevenir!\u201d \/ Deep Vein Thrombosis: \u201cKnowing is the best way to prevent it!\u201d","volume":"4","author":"LIBERATO C.C.G.","year":"2021","journal-title":"Brazilian Journal of Health Review"},{"issue":"2","key":"ref12","article-title":"Non-clinical toxicological analysis of dichlorinated phenylacrylate isomers: Ethyl (2E)-2-cyano-3-(2,6-dichlorophenyl)acrylate e Ethyl (2E)-2-cyano-3-(2,4-dichlorophenyl)acrylate","volume":"22","author":"LIMA Z.N.","year":"2024","journal-title":"Observat\u00f3rio de la Econom\u00eda Latinoamericana"},{"issue":"12","key":"ref13","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.3390\/molecules22122047","article-title":"Study on the anticoagulant or procoagulant activities of type II phenolic acid derivatives","volume":"22","author":"LUO X.","year":"2017","journal-title":"Molecules"},{"issue":"4","key":"ref14","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1021\/jf980737w","article-title":"Benzoic and cinnamic acid derivatives as antioxidants: structure\u2212activity relation","volume":"47","author":"NATELLA F.","year":"1999","journal-title":"Journal of Agricultural and Food Chemistry"},{"issue":"2","key":"ref15","doi-asserted-by":"crossref","first-page":"62","DOI":"10.5530\/fra.2024.2.7","article-title":"Antioxidants, radical scavengers, and their impact on oxidative stress","volume":"14","author":"OHIAGU F.O.","year":"2025","journal-title":"Free Radicals and Antioxidants"},{"issue":"1","key":"ref16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1590\/1983-084X\/12_165","article-title":"Determina\u00e7\u00e3o da capacidade antioxidante de produtos naturais in vitro pelo m\u00e9todo do DPPH: estudo de revis\u00e3o","volume":"17","author":"OLIVEIRA G.L.S.","year":"2015","journal-title":"Revista Brasileira de Plantas Medicinais"},{"issue":"19","key":"ref17","doi-asserted-by":"crossref","first-page":"6555","DOI":"10.3390\/molecules27196555","article-title":"Chemical composition, antioxidant activity, cytoprotective and in silico study of ethanolic extracts of bougainvillea \u00d7 buttiana (var. orange and rose)","volume":"27","author":"PETRICEVICH V.L.","year":"2022","journal-title":"Molecules"},{"issue":"1","key":"ref18","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s12906-018-2154-4","article-title":"Phenolic compounds as antioxidants and chemopreventive drugs from Streptomyces cellulosae strain TES17 isolated from rhizosphere of Camellia sinensis","volume":"18","author":"RANI R.","year":"2018","journal-title":"BMC Complementary and Alternative Medicine"},{"issue":"3","key":"ref19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/tme.12645","article-title":"Effects of L\u2010carnitine on the erythrocytes of stored human blood","volume":"30","author":"RAVIKUMAR S.","year":"2020","journal-title":"Transfusion Medicine"},{"key":"ref20","article-title":"Syringic and cinnamic acids antiradical\/antioxidant activities as R. ferruginea extract components and membrane physico-chemical influence","volume":"1220","author":"SANTOS D.M.","year":"2020","journal-title":"Journal of Molecular Structure"},{"issue":"3","key":"ref21","first-page":"175","article-title":"Estresse oxidativo em eritr\u00f3citos submetidos a 2,2- azobis amidinopropano (aaph): efeito antioxidante e anti- hemol\u00edtico do ch\u00e1 verde (Camellia sinensis)","volume":"12","author":"SCHMITZ W.O.","year":"2008","journal-title":"Arquivos de Ci\u00eancias da Sa\u00fade da UNIPAR"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ijbiomac.2019.03.059","article-title":"Secondary hemostasis studies of crude venom and isolated proteins from the snake Crotalus durissus terrificus","volume":"131","author":"SOUSA I.D.L.","year":"2019","journal-title":"International Journal of Biological Macromolecules"},{"key":"ref23","doi-asserted-by":"crossref","DOI":"10.1590\/1519-6984.244127","article-title":"Analysis of the toxicological and pharmacokinetic profile of Kaempferol-3-O-\u03b2-D-(6\u201d-E-p-coumaryl) glucopyranoside - Tiliroside: in silico, in vitro and ex vivo assay","volume":"83","author":"SOUSA A.P.","year":"2023","journal-title":"Brazilian Journal of Biology"},{"key":"ref24","article-title":"Phytochemistry, antifungal and antioxidant activity, and cytotoxicity of byrsonima gardneriana (A. Juss) extract","volume":"123","author":"SOUZA-MELO W.O.","year":"2021","journal-title":"Archives of Oral Biology"}],"container-title":["Brazilian Journal of Biology"],"original-title":["Potencial anticoagulante, antioxidante e citot\u00f3xico do \u00e1cido cin\u00e2mico e derivados sint\u00e9ticos"],"link":[{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_pdf&pid=S1519-69842026000100303&tlng=en","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:32:27Z","timestamp":1780054347000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_arttext&pid=S1519-69842026000100303&tlng=en"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":24,"alternative-id":["S1519-69842026000100303"],"URL":"https:\/\/doi.org\/10.1590\/1519-6984.303373","relation":{},"ISSN":["1678-4375","1519-6984"],"issn-type":[{"value":"1678-4375","type":"electronic"},{"value":"1519-6984","type":"print"}],"subject":[],"published":{"date-parts":[[2026]]},"article-number":"e303373"}}