{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T16:13:42Z","timestamp":1768407222097,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Science & Technology","award":["SR\/SO\/BB-0005\/2009"],"award-info":[{"award-number":["SR\/SO\/BB-0005\/2009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Many inhibitors have been discovered to target hypoxia-induced carbonic anhydrase IX (CAIX) due to its critical role in lung cancers. This study discovers a novel compound, 3-(E-3,4-dihydroxycinnamaoyloxyl)-2-hydroxypropyl-9Z,12Z-octadeca-9,12-dienoate, which is produced by the seagrass Cymodocea serrulata and has binding sites at CAIX that are distinct from those of current inhibitors. Methods: Compound and reference drug treatment for cell lines; Cell viability: MTT; Staining: Ao\/PI\/DAPI; MMP shifts and cell cycle: FACS; Gene and protein expression of CAIX, BAX, BAD: qPCR and Western blotting. Results: The compound binds to the CAIX protein, raises extracellular pH, and kills A549 cells [IC50: 11.61 \u00b5M], producing results that are lower than those of the reference drug doxorubicin [13.7 \u00b5M]. The substance depolarised the electrical potential of the mitochondrial membrane, caused S-phase arrest, and fragmented DNA. Additionally, it downregulated CAIX by 0.9 times while increasing apoptotic mRNA, BAX and BAD by 5.2 and 3.08 times, respectively, as demonstrated by qPCR. Between 0 and 24 h, the untreated hypoxic cells had a \u0394pHe of 0.15, but the compound-treated cells had a \u0394pHe of 0.6 indicative of intracellular acidosis. MD simulations verify the stability of the CAIX\u2013C1 complex for more than 100 ns, and in silico studies show a strong binding affinity of the molecule to CAIX [\u22127.55 kcal\/mol]. Conclusions: This implies that the amount of extracellular alkalosis was increased by the combination of treatment and hypoxia induction. As a result, when the cells were deprived of O2, the compound provided less defense against ROS. The compound binds to the glutamine and alanine amino acids at positions 242 and 392, respectively, at the central Zn atom of CAIX, which sets it apart from conventional sulphonamide CAIX inhibitors. This naturally occurring compound may be a potent CAIX inhibitor with newer binding sites, which could help treat hypoxic lung cancers.<\/jats:p>","DOI":"10.3390\/ph19010132","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:17:32Z","timestamp":1768292252000},"page":"132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Marine Anticancer Cinnamyloxyl Derivative with Unique Binding Sites at Carbonic Anhydrase IX (CAIX) Inhibits Adenocarcinomic A549 Cells"],"prefix":"10.3390","volume":"19","author":[{"given":"Shailaja","family":"Vommi Lakshmipathy","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Faculty of Biomedical Sciences and Technology (FBMS&T), Sri Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600116, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Vijayaraghavan Sathyanathan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Biomedical Sciences and Technology (FBMS&T), Sri Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600116, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohanapriya","family":"Dandapani Chinambedu","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Faculty of Biomedical Sciences and Technology (FBMS&T), Sri Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600116, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6758-443X","authenticated-orcid":false,"given":"Mohanraj","family":"Gopikrishnan","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhinand","family":"Ponneri Adithavarman","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Sri Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600116, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadras Panchatcharam","family":"Thyagarajan","sequence":"additional","affiliation":[{"name":"Vellore Institute of Technology (VIT), Vellore Campus, Tiruvalam Rd, Katpadi, Vellore 632014, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9323-7434","authenticated-orcid":false,"given":"Mary Elizabeth","family":"Gnanambal Krishnan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Biomedical Sciences and Technology (FBMS&T), Sri Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600116, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pries, A.R., Cornelissen, A.J.M., Sloot, A.A., Hinkeldey, M., Dreher, M.R., H\u00f6pfner, M., Dewhirst, M.W., and Secomb, T.W. 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