Cytotoxic, analgesic and anti-inflammatory activity of colchicine and its C-10 sulfur containing derivatives

Abstract

Abstract10-Alkylthiocolchicines have been obtained and characterized by spectroscopic methods and their biological activities as: cytotoxic, anti-inflammatory and analgesic activities have been tested. Cytotoxic activity against SKOV-3 ovarian cell line for 10-alkylthiocolchicine analogues was reported and tested compounds showed to be more active than commonly used doxorubicin. Some of tested C-10 alkylthiolated colchicines have been found to exhibit cytotoxicity at levels comparable to that of the natural product—colchicine. 10-Methylthiocolchicine has IC50 = 8 nM and 10-ethylthiocolchicine has IC50 = 47 nM in comparison to colchicine IC50 = 37 nM. Moreover for 10-alkylthioderivatives apoptosis test, cyclin B1 and cell cycle tests were performed. 10-n-Butylthiocolchicine was tested for anti-inflammatory and analgesic activities it showed to produce analgesic rather than anti-inflammatory effect.

Discovery and development of botanical natural products and their analogues as therapeutics for ovarian cancer

“…As a result, several colchicine SAR studies have been published to overcome known toxicity and increase antiproliferative activity. 96 Throughout the history of SAR studies surrounding colchicine, dozens of A, B, and C ring modification have been studied for their antiproliferative effects in various cancer cell lines such as lung, colon, colorectal, leukemia, breast, and ovarian (as reviewed by Ghawanmeh et al in 2020). 97 In Ghawanmeh's thorough review of colchicine SAR, they recapitulate that due to colchicine's low therapeutic index, SAR studies are vital to uncovering modifications that reduce unselective cytotoxicity and improve therapeutic activity.…”

Regioselective approach to colchiceine tropolone ring functionalization at C(9) and C(10) yielding new anticancer hybrid derivatives containing heterocyclic structural motifs

“…Recently, new colchicine-mimicking quinoline derivatives have been obtained which showed good tubulin polymerisation inhibitory effects as well as antiproliferative potency higher than that of 1 48 . Earlier functionalization of the 1 framework with sulphur substituents at C(10) also suggested the influence of the bulkiness of the thioether arm on the anticancer effects 49 .…”

Impact of Colchicine on Histology of Testis in Rats

“…In addition, it can arrest the meiotic divisions in murine (Liang et al, 1985). Colchicine is recently used for the treatment of covid 19 patients (Lopes et al, 2021;Scarsi et al, 2020) due to its anti-inflammatory action (Li et al, 2021;Kurek et al, 2021). It causes alterations in many inflammatory reactions as it prevents the aggregations of macrophages at the site of inflammation-reducing cytokine release and production of superoxide by neutrophils (Martínez et al, 2018;Kamel et al, 2021;Vitiello et al, 2022).…”