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Twenty\u2010two novel phthalazine derivatives were designed, synthesized, and evaluated against four human isoforms: hCA\u2005I, hCA\u2005II, hCA\u2005IX, and hCA\u2005XII. Compounds appeared to be very active mostly against hCA\u2005IX (<jats:bold>7<\/jats:bold>) and hCA\u2005I (<jats:bold>6<\/jats:bold>) isoforms being more potent than reference drug acetazolamide (<jats:bold>AAZ<\/jats:bold>). Some compounds appeared to be very selective with a selectivity index up to 13.8. Furthermore, docking was performed for some of these compounds on all isoforms to understand the possible interactions with the active site. Additionally, the most active compounds against hCA\u2005IX were subjected to cell viability assay. The anticancer activity of the compounds (<jats:bold>3\u2009a<\/jats:bold>\u2013<jats:bold>d<\/jats:bold>, <jats:bold>5\u2009d<\/jats:bold>, <jats:bold>5\u2009i<\/jats:bold>, and <jats:bold>5\u2009m<\/jats:bold>) was investigated using two human breast cancer cell lines, <jats:italic>i.\u2009e<\/jats:italic>. MCF\u20107 and MDA\u2010MB\u2010231 cells, and the normal counterpart, namely MCF10\u2010A cells.<\/jats:p>","DOI":"10.1002\/cmdc.202400147","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T13:53:25Z","timestamp":1715090005000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Phthalazine Sulfonamide Derivatives as Carbonic Anhydrase Inhibitors. Synthesis, Biological and <i>in silico<\/i> Evaluation"],"prefix":"10.1002","volume":"19","author":[{"given":"Andrea","family":"Angeli","sequence":"first","affiliation":[{"name":"NEUROFARBA Department, Sezione di Scienze Farmaceutiche Universit\u00e0 degli Studi di Firenze  Via Ugo Schiff 6 50019 Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthi","family":"Petrou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Aristotle University of Thessaloniki  54124 Thessaloniki Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viktor G.","family":"Kartsev","sequence":"additional","affiliation":[{"name":"InterBioScreen  142432 Chernogolovka Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandr","family":"Zubenko","sequence":"additional","affiliation":[{"name":"North-Caucasian Zonal Research Veterinary Institute  346406 Novocherkassk Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyudmila N.","family":"Divaeva","sequence":"additional","affiliation":[{"name":"North-Caucasian Zonal Research Veterinary Institute  346406 Novocherkassk Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Chekrisheva","sequence":"additional","affiliation":[{"name":"North-Caucasian Zonal Research Veterinary Institute  346406 Novocherkassk Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Iacopetta","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences University of Calabria  Via Pietro Bucci I-87036 Arcavacata di Rende Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Stefania","family":"Sinicropi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences University of Calabria  Via Pietro Bucci I-87036 Arcavacata di Rende Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samvel","family":"Sirakanyan","sequence":"additional","affiliation":[{"name":"Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia Institute of Fine Organic Chemistry of A.L. 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