{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T16:21:48Z","timestamp":1762273308777,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Princess Nourah bint Abdulrahman University","award":["PNURSP2024R403"],"award-info":[{"award-number":["PNURSP2024R403"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The goal of this study was directed to synthesize a novel class of annulated compounds containing difuro[3,2-c:3\u2032,2\u2032-g]chromene. Friedl\u00e4nder condensation of o-aminoacetyl derivative 3 was performed with some active methylene ketones, namely, 1,3-cyclohexanediones, pyrazolones, 1,3-thiazolidinones and barbituric acids, furnished furochromenofuroquinolines (4,5), furochromenofuropyrazolopyridines (6\u20138), furochromenofurothiazolopyridines (9,10) and furochromenofuropyridopyrimidines (11, 12), respectively. Also, condensation of substrate 3 with 5-amine-3-methyl-1H-pyrazole and 6-amino-1,3-dimethyluracil, as cyclic enamines, resulted in polyfused systems 13 and 14, respectively. In vitro antimicrobial efficiency of the prepared heterocycles against microbial strains exhibited variable inhibition action, where compound 3 was the most effective against all kinds of microorganisms. A significant cytotoxic activity was seen upon the annulation of the starting compound with thiazolopyridine (9 and 10) as well as pyridopyrimidine moieties (11, 12 and 14). The spectroscopic and analytical results were used to infer the structures of the novel synthesized compounds.<\/jats:p>","DOI":"10.3390\/molecules29102319","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T06:14:42Z","timestamp":1715753682000},"page":"2319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis, Characterization and Antimicrobial and Anticancer Evaluations of Some Novel Heteroannulated Difuro[3,2-c:3\u2032,2\u2032-g]Chromenes"],"prefix":"10.3390","volume":"29","author":[{"given":"Najla A.","family":"Alshaye","sequence":"first","affiliation":[{"name":"Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdy A.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo 11711, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0138-9794","authenticated-orcid":false,"given":"Al-Shimaa","family":"Badran","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo 11711, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1055\/s-0028-1099916","article-title":"A micro-method for the estimation of khellin in presence of other constituents of Ammi visnaga fruits","volume":"16","author":"Balbaa","year":"1968","journal-title":"Planta Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1080\/14786419.2021.1956924","article-title":"Khellin and visnagin in different organs of Ammi visnaga and Ammi majus","volume":"37","author":"Beyazit","year":"2023","journal-title":"Nat. Prod. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.ejmech.2014.12.001","article-title":"Synthesis, reactions and biological activities of furochromones: A review","volume":"90","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.phymed.2009.10.011","article-title":"An aqueous extract of Ammi visnaga fruits and its constituents khellin and visnagin prevent cell damage caused by oxalate in renal epithelial cells","volume":"17","author":"Vanachayangkul","year":"2010","journal-title":"Phytomedicine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1016\/j.jcrysgro.2009.02.027","article-title":"Effect of supersaturation ratio and Khella extract on nucleation and morphology of kidney stones","volume":"311","author":"Daosukho","year":"2009","journal-title":"J. Cryst. Growth"},{"key":"ref_6","first-page":"393","article-title":"Synthesis of some chromones and angular furochromones of expected pharmacological activities","volume":"29","author":"Hassib","year":"1988","journal-title":"Egypt J. Pharm. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/0002-8703(49)91131-X","article-title":"The coronary vasodilator action of khellin","volume":"37","author":"Anrep","year":"1949","journal-title":"Am. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mgamat, F., Benaddou, M., Haida, S., Oubihi, A., El Ibaoui, H., Zouhair, R., Kribii, A., El Ayadi, R., and Hmoun, D. (2023). Phytochemical evaluation, antioxidant, and antibacterial activity of extracts of Ammi visnaga Lam. Chem. Data Collect., 48.","DOI":"10.1016\/j.cdc.2023.101096"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s43440-023-00452-w","article-title":"Comparative study on the impacts of visnagin and its methoxy derivative khellin on human lymphocyte proliferation and Th1\/Th2 balance","volume":"75","author":"Askari","year":"2023","journal-title":"Pharmacol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.3390\/molecules16031956","article-title":"Synthesis of new visnagen and khellin furochromone pyrimidine derivatives and their anti-Inflammatory and analgesic activity","volume":"16","author":"Youssef","year":"2011","journal-title":"Molecules"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s13337-022-00803-w","article-title":"Ammi-visnaga extract; a novel phyto-antiviral agent against bovine rotavirus","volume":"34","author":"Harb","year":"2023","journal-title":"Virus Disease"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1248\/cpb.58.1148","article-title":"Synthesis and anticonvulsant activity of certain substituted furochromone, benzofuran and flavone derivatives","volume":"58","author":"Ragab","year":"2010","journal-title":"Chem. Pharm. Bull."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/1011-1344(90)85165-S","article-title":"Photosensitization of DNA of defined sequence by furochromones, khellin and visnagin","volume":"7","author":"Trabalzini","year":"1990","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.13005\/bpj\/2500","article-title":"Immuno-Modulatory, Anti-Psoriatic Effects and Furanochromone (Khellin and Visnagin) Contents of Ammi visnaga (L.) Hydroethanolic extract","volume":"15","author":"Lahna","year":"2022","journal-title":"Biomed. Pharmac. J."},{"key":"ref_15","first-page":"820","article-title":"Ammi visnaga L. and Nanocarrier Approaches in the Treatment of Skin Diseases","volume":"26","author":"Abdo","year":"2022","journal-title":"J. Res. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zaher, A., Aslam, R., Lee, H.-S., Khafouri, A., Boufellous, M., Alrashdi, A.A., El aoufir, Y., Lgaz, H., and Ouhssine, M. (2022). A combined computational & electrochemical exploration of the Ammi visnaga L. extract as a green corrosion inhibitor for carbon steel in HCl solution. Arab. J. Chem., 15.","DOI":"10.1016\/j.arabjc.2021.103573"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Abdel Halim, S., and Ibrahim, M.A. (2023). Quantum computational, Spectroscopic investigations on benzofuranylcarbonylpyrazolopyridine by DFT\/TD-DFT: Synthesis, Structure, NBO and NLO research. J. Mol. Struct., 1293.","DOI":"10.1016\/j.molstruc.2023.136201"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"389","DOI":"10.3987\/REV-16-852","article-title":"Chemical reactions of furochromones, visnagin and khellin","volume":"94","author":"Ibrahim","year":"2017","journal-title":"Heterocycles"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.3987\/COM-20-14273","article-title":"Chemical transformations with 4,9-dimethoxy-5-oxo-5H-furo[3,2-g] chromene-6-carbonitrile: Construction and antimicrobial evaluation of the novel heteroannulated furochromenopyridines","volume":"100","author":"Ibrahim","year":"2020","journal-title":"Heterocycles"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1002\/jhet.4308","article-title":"New synthetic strategy for Friedlander condensation of 4-amino-2-oxo-2H-chromene-3-carbaldehyde by heterogeneous catalysis","volume":"58","author":"Jadhav","year":"2021","journal-title":"J. Heterocycl. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ghosh, S., Krishnan, J., Karthik, V., Rana, A., Dhakshinamoorthy, A., and Biswas, S. (2022). Friedlander condensation reaction catalyzed by hafnium-based metal-organic framework. Mol. Catal., 533.","DOI":"10.1016\/j.mcat.2022.112748"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6485","DOI":"10.1080\/10406638.2021.1984258","article-title":"Dioxovanadium(V) Complex Incorporating Tridentate ONO Donor Aminobenzohydrazone Ligand: Synthesis, Spectral Characterization and Application as a Homogeneous Lewis Acid Catalyst in the Friedl\u00e4nder Synthesis of Substituted Quinolines","volume":"42","author":"Kargar","year":"2022","journal-title":"Polycycl. Aromat. Compd."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1002\/jhet.2733","article-title":"Chemical reactivity of 4,9-dimethoxy-5-oxo-5H-furo[3,2-g] chromene-6-carboxaldehyde toward some nucleophilic reagents","volume":"54","author":"Ibrahim","year":"2017","journal-title":"J. Heterocycl. Chem."},{"key":"ref_24","unstructured":"Allehyani, E.S. Design, characterization and antimicrobial efficiency of novel annulated furo[3\u2033,2\u2033:6\u2032,7\u2032]chromeno[3\u2032,4\u2032:4,5] furo[3,2-b]pyridines, Polycycl. Arom. Compds., in press."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.tetlet.2019.03.041","article-title":"Construction of new heteroacenes based on benzo[b]thieno [2,3-d] thiophene\/quinoline or 1,8-naphthyridine systems using the Friedl\u00e4nder reaction","volume":"60","author":"Irgashev","year":"2019","journal-title":"Tetrahedron Lett."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hussain, Z., Ibrahim, M.A., El-Gohary, N.M., and Badran, A. (2022). Synthesis, characterization, DFT, QSAR, antimicrobial, and antitumor studies of some novel pyridopyrimidines. J. Mol. Struct., 1269.","DOI":"10.1016\/j.molstruc.2022.133870"},{"key":"ref_27","first-page":"178","article-title":"The Determination of Bacterial Sensitivity to Antibiotics","volume":"59","author":"Gould","year":"1952","journal-title":"Edinb. Med. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/10\/2319\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:42:43Z","timestamp":1760107363000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/10\/2319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":28,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["molecules29102319"],"URL":"https:\/\/doi.org\/10.3390\/molecules29102319","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2024,5,15]]}}}