{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:12:40Z","timestamp":1788250360974,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["SNIH-RO-HRT01-2302-KSU-36598045"],"award-info":[{"award-number":["SNIH-RO-HRT01-2302-KSU-36598045"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Two series of pyrazolo[3,4-b]pyridine derivatives, 9a\u2013h and 14a\u2013h, are synthesized and evaluated for their anti-cancer potency towards Hela, MCF7, and HCT-116 cancer cell lines. Compound 9a showed the highest anticancer activity with IC50 = 2.59 \u00b5M against Hela when compared with doxorubicin (IC50 = 2.35 \u00b5M). Compound 14g revealed cytotoxicity IC50 = 4.66 and 1.98 \u00b5M towards MCF7 and HCT-116 compared to doxorubicin with IC50 = 4.57 and 2.11 \u00b5M, respectively. Compound 9a exhibited cell cycle arrest at the S phase for Hela, whereas 14g revealed an arresting cell cycle for MCF7 at G2\/M phase and an arresting cell cycle at S phase in HCT-116. In addition, 9a induced a significant level of early and late apoptosis in Hela when compared with the control cells, whereas 14g induced an apoptosis in MCF7 and HCT-116, respectively. Compounds 9a (IC50 = 26.44 \u00b1 3.23 \u00b5M) and 14g (IC50 = 21.81 \u00b1 2.96 \u00b5M) showed good safety profiles on normal cell line WI-38. Compounds 9a and 14g showed good inhibition activity towards CDK2, with IC50 = 1.630 \u00b1 0.009 and 0.460 \u00b1 0.024 \u00b5M, respectively, when compared with ribociclib (IC50 = 0.068 \u00b1 0.004). Furthermore, 9a and 14g showed inhibitory activity towards CDK9 with IC50 = 0.262 \u00b1 0.013 and 0.801 \u00b1 0.041 \u00b5M, respectively, related to IC50 of ribociclib = 0.050 \u00b1 0.003. Docking study for 9a and 14g exhibited good fitting in the CDK2 and CDK9 active sites.<\/jats:p>","DOI":"10.3390\/molecules28176428","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T10:24:30Z","timestamp":1693823070000},"page":"6428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Synthesis and In Vitro Anticancer Activity of Novel 4-Aryl-3-(4-methoxyphenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridines Arrest Cell Cycle and Induce Cell Apoptosis by Inhibiting CDK2 and\/or CDK9"],"prefix":"10.3390","volume":"28","author":[{"given":"Basma S.","family":"Almansour","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faizah A.","family":"Binjubair","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa A.-M.","family":"Abdel-Aziz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara T.","family":"Al-Rashood","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1126\/science.294.5542.502","article-title":"Cycling toward Stockholm","volume":"294","author":"Balter","year":"2001","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.phrs.2016.03.012","article-title":"Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs","volume":"107","author":"Roskoski","year":"2016","journal-title":"Pharmacol. 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