Synthesis of novel thiazoles bearing lupeol derivatives as potent anticancer and anti-inflammatory agents

• Published in: Natural product research Vol. 38; no. 13; pp. 2207 - 2214
• Main Authors: Narendar, Kummari, Rao, B. Sambasiva, Tirunavalli, Satyakrishna, Jadav, Surender Singh, Andugulapati, Sai Balaji, Ramalingam, Vaikundamoorthy, Babu, K. Suresh
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.07.2024; Taylor & Francis Ltd
• Subjects: Animals; anti-inflammatory; Anti-inflammatory agents; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; anticancer; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic drugs; Apoptosis; Apoptosis - drug effects; BAX gene; BAX protein; Bcl-2 protein; Biological activity; Biological effects; Cancer; Cell cycle; Cell Line, Tumor; Chemotherapy; Cytotoxicity; Diabetes mellitus; Gene expression; Humans; Inflammatory diseases; Interleukin-6 - metabolism; Lupanes; Lupeol; Metabolites; Mice; Molecular Structure; Oxazoles; Pentacyclic Triterpenes - chemistry; Pentacyclic Triterpenes - pharmacology; RAW 264.7 Cells; S phase; Terpenes; Thiazoles; Thiazoles - chemistry; Thiazoles - pharmacology; Vimentin; anti-inflammatory; oxazoles; thiazoles; Lupeol; anticancer
• ISSN: 1478-6419; 1478-6427; 1478-6427
• DOI: 10.1080/14786419.2023.2166042

Lupeol is one of the most important metabolite in the class of terpenoids and possess excellent anticancer, anti-inflammatory, anti-diabetic activities etc. In the present study, the different thiazoles and oxazoles bearing lupeol derivatives were prepared to enhance their biological activity. Initially, the in vitro cytotoxic activity results showed that the synthesized lupeol derivatives (9a-9j and 10a-10e) showed significant activity against various cancer cells and the compounds 9h and 10b exhibited excellent activity against CAL27 cells. Further, these compounds 9h and 10b arrest the cell cycle at S phase and induce the late apoptosis in CAL27 cells by downregulating the BcL2 and vimentin expression and upregulating the Bax gene expression. Moreover, the lupeol derivatives showed dose-dependent anti-inflammatory activity by inhibiting the secretion of IL-6 cytokines in LPS-induced Raw 264.7 cells. Together, these results clearly indicated that the thiazoles and oxazoles bearing lupeol derivatives can used as chemotherapeutic drugs against cancer and inflammatory diseases.