Antiproliferative and apoptotic activity of new indazole derivatives as potential anticancer agents. Issue 12 (18th August 2020)

• Record Type: Journal Article
• Authors: Laghchioua, Fatima E.; Kouakou, Assoman; Eddahmi, Mohammed; Viale, Maurizio; Monticone, Massimiliano; Gangemi, Rosaria; Maric, Irena; El Ammari, Lahcen; Saadi, Mohamed; Baltas, Michel; Kandri Rodi, Youssef; Rakib, El Mostapha
• Is Part Of: Archiv der Pharmazie. Volume 353:Issue 12(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-08-18
• Subjects: antiproliferative activity -- apoptosis -- cell cycle -- polysubstituted indazoles; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202000173
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: To develop potent and selective anticancer agents, a series of novel polysubstituted indazoles was synthesized and evaluated for their in vitro antiproliferative and apoptotic activities against two selected human cancer cell lines (A2780 and A549). Several compounds showed an interesting antiproliferative activity, with IC50 values ranging from 0.64 to 17 µM against both cell lines. The most active indazoles were then tested in different pharmacological dilution conditions, adding five new cell lines (A2780, A549, IMR32, MDA‐MB‐231, and T47D) as targets, confirming their antiproliferative activity. Furthermore, selected compounds were able to trigger apoptosis to a significant extent and to cause, in part, a block of cells in the S phase of the cell cycle, with a concomitant decrease of cells in the G2/M and/or G0/G1 phases and the generation of hypodiploid peaks. However, molecule 7d caused a great increase of cells in G2/M and the appearance of polyploid cells. Altogether, our results suggest a good pharmacological activity for our selected polysubstituted indazoles, which are suggestive of a preferential mechanism of action as cell cycle‐specific antimetabolites or as an inhibitor of enzyme activities involved in DNA synthesis, except for 7d, which, on the contrary, seems to have a mechanism involving the microtubule system. Abstract : A new series of 2‐(aryl)‐2‐(7(4)‐(arylsulfonyl)oxime‐1‐alkyl‐1 H ‐indazol‐7(4)‐ylidenes) was synthesized and screened for their antiproliferative and apoptotic activities. Also, 95% of these compounds showed a quite interesting antiproliferative activity, with IC50 values ranging from 0.42 to 17 µM against both cell lines. In particular, compounds 5a, 5c, 5f, 7d, and 8c showed an excellent anticancer activity. Notably, compound 8c was found as potently arresting the cell cycle at the S phase.