Novel pyrazolo3,4-dpyrimidine derivatives inhibit human cancer cell proliferation and induce apoptosis by ROS generation

Gaonkar, S and Savanur, MA and Nadaf, AA and Najare, MS and Mantur, S and Garbhagudi, M and Mulla, SI and Khazi, IAM (2020) Novel pyrazolo3,4-dpyrimidine derivatives inhibit human cancer cell proliferation and induce apoptosis by ROS generation. In: Archiv der Pharmazie, 353 (4).

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Abstract

to explore the potential of pyrazolo[3,4-d]pyrimidine derivatives as antiproliferative agents. In vitro anticancer screening of selected compounds was done by the National Cancer Institute's Developmental Therapeutics Programme against a panel of 60 cancer cell lines. The lead compound PP-31d considerably inhibited the growth of cancer cells, such as NCI-H460 (non-small-cell lung cancer), OVCAR-4 (ovarian cancer), 786-0 (renal cancer), A549 (non-small-cell lung cancer), and ACHN (renal cancer), showing strong anticancer potential, among other derivatives. Kinetic studies of PP-31d on NCI-H460 cells revealed a dose-dependent effect with an IC50 of 2 µM. The observed inhibition by PP-31d is attributed to the generation of reactive oxygen species and the subsequent induction of cellular apoptosis, as evidenced by the increase in the hypodiploid (subG1) population, the early apoptotic cell population, and caspase-3/7 activity, the loss of the mitochondrial membrane potential, and the degradation of nuclear DNA. Collectively, our results demonstrated that pyrazolo[3,4-d]pyrimidine derivatives inhibit cancer cell proliferation by inducing apoptosis and, thus, have the potential to be further explored for anticancer properties

Item Type:	Journal Article
Publication:	Archiv der Pharmazie
Publisher:	Wiley-VCH Verlag
Additional Information:	The copyright for this article belongs to the Wiley-VCH Verlag.
Keywords:	1 (1,1' biphenyl) 4 yl 3 methyl 1,5 dihydro 1h pyrazolo3,4 dpyrimidin 4 amine; 1 (1,1' biphenyl) 4 yl 3 methyl 1,5 dihydro 4h pyrazolo3,4 dpyrimidin 4 one; 1 (1,1' biphenyl) 4 yl 3 methyl 6 phenyl 1,5 dihydro 1h pyrazolo3,4 dpyrimidin 4 amine; 1 (1,1' biphenyl) 4 yl 6 benzyl 3 methyl 1,5 dihydro 1h pyrazolo3,4 dpyrimidin 4 amine; 1 4' ethyl (1,1' biphenyl) 4 yl 3 methyl 1,5 dihydro 1h pyrazolo3,4 dpyrimidin 4 amine; 1 4' ethyl (1,1' biphenyl) 4 yl 3 methyl 1,5 dihydro 4h pyrazolo3,4 dpyrimidin 4 one; 1 4' ethyl (1,1' biphenyl) 4 yl 3 methyl 6 phenyl 1,5 dihydro 1h pyrazolo3,4 dpyrimidin 4 amine; 3 methyl 1 4' (trifluoromethoxy)(1,1' biphenyl) 4 yl 1,5 dihydro 4h pyrazolo3,4 dpyrimidin 4 one; 3 methyl 1 4' (trifluoromethoxy)(1,1' biphenyl) 4 yl 1h pyrazolo3,4 dpyrimidin 4 amine; 3 methyl 6 phenyl 1 4' (trifluoromethoxy)(1,1' biphenyl) 4 yl 1h pyrazolo3,4 dpyrimidin 4 amine; 6 benzyl 1 4' ethyl (1,1' biphenyl) 4 yl 3 methyl 1,5 dihydro 1h pyrazolo3,4 dpyrimidin 4 amine; 6 benzyl 3 methyl 1 4' (trifluoromethoxy)(1,1' biphenyl) 4 yl 1h pyrazolo3,4 dpyrimidin 4 amine; caspase 3; caspase 7; cell nucleus DNA; cytotoxic agent; pyrazolo3,4 dpyrimidine derivative; reactive oxygen metabolite; unclassified drug; antineoplastic agent; pyrazole derivative; pyrazolo(3,4-d)pyrimidine; pyrimidine derivative; reactive oxygen metabolite, 786-O cell line; A-549 cell line; ACHN cell line; antineoplastic activity; antiproliferative activity; apoptosis; Article; cancer inhibition; controlled study; DNA degradation; drug cytotoxicity; drug potency; drug screening; embryo; enzyme activity; female; human; human cell; IC50; in vitro study; liquid chromatography-mass spectrometry; mitochondrial membrane potential; NCI-H460 cell line; OVCAR-4 cell line; priority journal; X ray diffraction; apoptosis; cell cycle; cell proliferation; cell survival; chemical structure; chemistry; dose response; drug effect; metabolism; molecular model; structure activity relation; synthesis; tumor cell culture, Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Membrane Potential, Mitochondrial; Models, Molecular; Molecular Structure; Pyrazoles; Pyrimidines; Reactive Oxygen Species; Structure-Activity Relationship; Tumor Cells, Cultured
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	01 Feb 2023 07:40
Last Modified:	01 Feb 2023 07:40
URI:	https://eprints.iisc.ac.in/id/eprint/79669

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