Synthesis and Cytotoxicity of Sulfanyl, Sulfinyl and Sulfonyl Group Containing Ursane Conjugates with 1,3,4‐Oxadiazoles and 1,2,4‐Triazoles

Abstract

A library of novel sulfanyl, sulfinyl, and sulfonyl groupcontaining ursane conjugates with 1,3,4-oxadiazoles and 1,2,4triazoles were designed and obtained. The target compounds were synthesized by alkylation of the corresponding azolebased thiones followed by S-selective oxidation. The expected sulfoxides and sulfones were obtained depending on the applied excess of mCPBA without oxidation of the ursane double bond. The novel products were studied for their antiproliferative activity on cell lines MCF7 (breast cancer), U-87 MG (glioblastoma multiform cells), A549 (lung carcinoma), and U-87 MG (hepatocarcinoma), using immortalized human fibroblasts hTERT as non-cancer control. Oxadiazole-derived methylsulfones possessed the most notable cytotoxicity, while the sulfanyl group containing ursane conjugates with 1,2,4-triazoles 7 g, 7 h exhibited the best selectivity and antiproliferative activity, superior to ursolic acid and starting azole-based thiones. Possible mechanism of action of thioethers 7 g, 7 h was studied using molecular modeling.

Enhanced Cytotoxicity and Antimelanoma Activity of Novel Semisynthetic Derivatives of Betulinic Acid with Indole Conjugation

“…However, when considering medicinal applications, the use of BI as a possible therapeutic agent is hampered by its restricted solubility and diminished bioavailability in vivo [ 52 ]. Therefore, BI has been used as a scaffold for several semisynthetic derivatives that exhibit promise as enhanced pharmaceutical agents [ 36 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. The indole scaffold has significant importance within the domains of medical chemistry and organic chemistry [ 61 , 62 , 63 , 64 ].…”