Synthesis of Canthardin Sulfanilamides and Their Acid Anhydride Analogues via a Ring-Opening Reaction of Activated Aziridines and Their Associated Pharmacological Effects

Abstract

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.

Crystallization-Based Synthetic Route to Antimalarial Agent BRD5018: Diazocene Ring Formation via a Staudinger-aza-Wittig Reaction on an Azetidine-Ribose Template

“…In the event, a treatment of the bis-mesylate with K-phthalimide in dimethylformamide (DMF) at ambient temperature smoothly afforded a single product (>90% yield) from this reaction, which was found to be the desired azetidine 39 with all-cis stereochemistry (Scheme 5). 16 The isolation of 39 as a crystalline solid could be induced by a direct addition of water to the reaction mixture. The crystallinity of 39 provided a key quality control point at this juncture of the synthesis.…”

Norbornene and Related Structures as Scaffolds in the Search for New Cancer Treatments

“…Other relevant derivatives are the cantharidin-sulfanil-Figure 9. Norcantharidin , cantharidin [119][120][121][122][123][124][125][126][127][128][129][130][131], and related molecules.…”

“…The new designed analogue methyl cantharidimide (Figure 9, 9i) was effective against endocervical adenocarcinoma cell line KB-C2 overexpressing ABCB1 and against human SDHB knockout HEK-293 cell line, which overexpresses ABCG2, as well as cisplatin-resistant cells, such as KCB-4 [128]. Other relevant derivatives are the cantharidin-sulfanilamides (Figure 9, 9j) that exhibited anti-HL-60 and anti-Hep3B cell activities [129].…”

Drug Design and Discovery: Principles and Applications

“…In the article “Synthesis of Canthardin Sulfanilamides and Their Acid Anhydride Analogues via a Ring-Opening Reaction of Activated Aziridines and Their Associated Pharmacological Effects” [ 26 ], Mei-Hsiang Lin and coworkers reported their investigation to find new cantharidinimides and related imides containing the sulfonamide group. The modification of cantharidinimide by means of the reaction of activated aziridine ring opening led to the discovery of a novel class of antitumor compounds.…”

“…They found that the most potent cytostatic compound, N -cantharidinimido-sulfamethazine, exhibited anti-HL-60 and anti-Hep3B cell activities. Detailed results of their investigation are presented in the article [ 26 ].…”