title: Synthesis of Canthardin Sulfanilamides and Their Acid Anhydride Analogues via a Ring-Opening Reaction of Activated Aziridines and Their Associated Pharmacological Effects.
abstract: The cantharidinimide derivatives, 5a-h, including sulfanilamides containing pyrimidyl, pyrazinyl, hydrogen, thiazolyl, and oxazolyl groups were synthesized. Modification of cantharidinimide by means of the reaction of activated aziridine ring opening led to the discovery of a novel class of antitumor compounds. The analogues 10i-k, 11l-n, 12o-p, and 16q-s were obtained from treating cantharidinimide 6 and analogues (7, 8, and 13) with activated aziridines, which produced a series of ring-opened products including normal and abnormal types. Some of these compounds showed cytotoxic effects in vitro against HL-60, Hep3B, MCF7, and MDA-MB-231 cancer cells. The most potent cytostatic compound, N-cantharidinimido-sulfamethazine (5a), exhibited anti-HL-60 and anti-Hep3B cell activities. Two compounds 5g and 5h displayed slight effects on the Hep3B cell line, while the other compounds produced no response in these four cell lines.
authors.affiliation: School of Respiratory Therapy, Taipei Medical University, Taipei 11031, Taiwan. llchiang@tmu.edu.tw.|Chest Medicine Department, Shuang-Ho Hospital, Taipei Medical University, Taipei 11031, Taiwan. llchiang@tmu.edu.tw.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Chiang
authors.affiliation: Gerontology Health Management, College of Nursing, Taipei Medical University, Taipei 11031, Taiwan. Ingjy@tmu.edu.tw.
authors.forename: Ing-Jy
authors.initials: IJ
authors.lastname: Tseng
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan. lpy0620@tmu.edu.tw.
authors.forename: Pen-Yuan
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan. amel@tmu.edu.tw.
authors.forename: Shiow-Yunn
authors.initials: SY
authors.lastname: Sheu
authors.affiliation: Department of Chemistry, Tam-Kang University, Danshui 25137, New Taipei City, Taiwan. rocketqueenohya@hotmail.com.
authors.forename: Ching-Tung
authors.initials: CT
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan. jay4273803@hotmail.com.
authors.forename: Yun-Han
authors.initials: YH
authors.lastname: Hsieh
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan. m301101003@tmu.edu.tw.
authors.forename: Yi-Jing
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan. m301101001@tmu.edu.tw.
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan. mhl00001@tmu.edu.tw.
authors.forename: Mei-Hsiang
authors.initials: MH
authors.lastname: Lin
mesh_terms: D000812:Anhydrides / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001388:Aziridines / Q000737:chemistry*; D002193:Cantharidin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D010080:Oxazoles / Q000737:chemistry; D011720:Pyrazoles / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D013329:Structure-Activity Relationship; D013424:Sulfanilamides / Q000138:chemical synthesis / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry
chemical_list: D000812:Anhydrides; D000970:Antineoplastic Agents; D001388:Aziridines; D010080:Oxazoles; D011720:Pyrazoles; D011743:Pyrimidines; D013424:Sulfanilamides; D013844:Thiazoles; D002193:Cantharidin
keywords: cantharidin; cantharidinimide; methylsulfanylaziridine