Synthesis of Canthardin Sulfanilamides and Their Acid Anhydride Analogues via a Ring-Opening Reaction of Activated Aziridines and Their Associated Pharmacological Effects
Ling-Ling Chiang,
Ing-Jy Tseng,
Pen-Yuan Lin,
Shiow-Yunn Sheu,
Ching-Tung Lin,
Yun-Han Hsieh,
Yi-Jing Lin,
Hsiao-Ling Chen,
Mei-Hsiang Lin
Affiliations
Ling-Ling Chiang
School of Respiratory Therapy, Taipei Medical University, Taipei 11031, Taiwan
Ing-Jy Tseng
Gerontology Health Management, College of Nursing, Taipei Medical University, Taipei 11031, Taiwan
Pen-Yuan Lin
Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
Shiow-Yunn Sheu
Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
Ching-Tung Lin
Department of Chemistry, Tam-Kang University, Danshui 25137, New Taipei City, Taiwan
Yun-Han Hsieh
Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
Yi-Jing Lin
Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
Hsiao-Ling Chen
Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
Mei-Hsiang Lin
Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
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.
