Antiproliferative and apoptotic activity of new indazole derivatives as potential anticancer agents
Fatima E. Laghchioua
Laboratory of Organic and Analytical Chemistry, Faculty of Sciences and Technics, Sultan Moulay Slimane University, Béni-Mellal, Morocco
Search for more papers by this authorAssoman Kouakou
Laboratory of Organic and Analytical Chemistry, Faculty of Sciences and Technics, Sultan Moulay Slimane University, Béni-Mellal, Morocco
Search for more papers by this authorMohammed Eddahmi
Laboratory of Organic and Analytical Chemistry, Faculty of Sciences and Technics, Sultan Moulay Slimane University, Béni-Mellal, Morocco
Search for more papers by this authorMaurizio Viale
IRCCS Ospedale Policlinico San Martino, U.O.C. Bioterapie, Genova, Italy
Search for more papers by this authorMassimiliano Monticone
IRCCS Ospedale Policlinico San Martino, U.O.C. Bioterapie, Genova, Italy
Search for more papers by this authorRosaria Gangemi
IRCCS Ospedale Policlinico San Martino, U.O.C. Bioterapie, Genova, Italy
Search for more papers by this authorIrena Maric
IRCCS Ospedale Policlinico San Martino, U.O.C. Bioterapie, Genova, Italy
Search for more papers by this authorLahcen El Ammari
Laboratoire de Chimie Appliquée des Matériaux, Centre des Sciences des Matériaux, Faculty of Science, Mohammed V University, Rabat, Morocco
Search for more papers by this authorMohamed Saadi
Laboratoire de Chimie Appliquée des Matériaux, Centre des Sciences des Matériaux, Faculty of Science, Mohammed V University, Rabat, Morocco
Search for more papers by this authorMichel Baltas
Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, UMR-CNRS, Université Paul Sabatier, Toulouse, France
Search for more papers by this authorYoussef Kandri Rodi
Laboratory of Applied Organic Chemistry, Faculty of Sciences and Technics, Sidi Mohamed Ben Abdallah University, Fez, Morocco
Search for more papers by this authorCorresponding Author
El Mostapha Rakib
Laboratory of Organic and Analytical Chemistry, Faculty of Sciences and Technics, Sultan Moulay Slimane University, Béni-Mellal, Morocco
Correspondence El Mostapha Rakib, Laboratory of Organic and Analytical Chemistry, Faculty of Sciences and Technics, Sultan Moulay Slimane University, B.P. 523, Béni-Mellal, Morocco.
Email: [email protected]
Maurizio Viale, IRCCS Ospedale Policlinico San Martino, U.O.C. Bioterapie, L.go R. Benzi 10, 16132 Genova, Italy.
Email: [email protected]
Search for more papers by this authorFatima E. Laghchioua
Laboratory of Organic and Analytical Chemistry, Faculty of Sciences and Technics, Sultan Moulay Slimane University, Béni-Mellal, Morocco
Search for more papers by this authorAssoman Kouakou
Laboratory of Organic and Analytical Chemistry, Faculty of Sciences and Technics, Sultan Moulay Slimane University, Béni-Mellal, Morocco
Search for more papers by this authorMohammed Eddahmi
Laboratory of Organic and Analytical Chemistry, Faculty of Sciences and Technics, Sultan Moulay Slimane University, Béni-Mellal, Morocco
Search for more papers by this authorMaurizio Viale
IRCCS Ospedale Policlinico San Martino, U.O.C. Bioterapie, Genova, Italy
Search for more papers by this authorMassimiliano Monticone
IRCCS Ospedale Policlinico San Martino, U.O.C. Bioterapie, Genova, Italy
Search for more papers by this authorRosaria Gangemi
IRCCS Ospedale Policlinico San Martino, U.O.C. Bioterapie, Genova, Italy
Search for more papers by this authorIrena Maric
IRCCS Ospedale Policlinico San Martino, U.O.C. Bioterapie, Genova, Italy
Search for more papers by this authorLahcen El Ammari
Laboratoire de Chimie Appliquée des Matériaux, Centre des Sciences des Matériaux, Faculty of Science, Mohammed V University, Rabat, Morocco
Search for more papers by this authorMohamed Saadi
Laboratoire de Chimie Appliquée des Matériaux, Centre des Sciences des Matériaux, Faculty of Science, Mohammed V University, Rabat, Morocco
Search for more papers by this authorMichel Baltas
Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, UMR-CNRS, Université Paul Sabatier, Toulouse, France
Search for more papers by this authorYoussef Kandri Rodi
Laboratory of Applied Organic Chemistry, Faculty of Sciences and Technics, Sidi Mohamed Ben Abdallah University, Fez, Morocco
Search for more papers by this authorCorresponding Author
El Mostapha Rakib
Laboratory of Organic and Analytical Chemistry, Faculty of Sciences and Technics, Sultan Moulay Slimane University, Béni-Mellal, Morocco
Correspondence El Mostapha Rakib, Laboratory of Organic and Analytical Chemistry, Faculty of Sciences and Technics, Sultan Moulay Slimane University, B.P. 523, Béni-Mellal, Morocco.
Email: [email protected]
Maurizio Viale, IRCCS Ospedale Policlinico San Martino, U.O.C. Bioterapie, L.go R. Benzi 10, 16132 Genova, Italy.
Email: [email protected]
Search for more papers by this authorAbstract
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.
Supporting Information
| Filename | Description |
|---|---|
| ardp202000173-sup-0001-ArchPharm_SupplMat_InChI_2020Rakib.doc70.5 KB | Supporting information |
| ardp202000173-sup-0002-Supplementary_information_2020_Rakib_mod.docx4.6 MB | Supporting information |
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