Facile synthesis and in-vitro antitumor activity of some pyrazolo[3,4-b]pyridines and pyrazolo[1,5-a]pyrimidines linked to a thiazolo[3,2-a]benzimidazole moiety.
The key precursor E-3-(N,N-dimethylamino)-1-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)prop-2-en-1-one 4 was synthesized in good yield using Gold's reagent. The reaction of enaminone 4 with 5-amino-3-aryl-1-phenylpyrazoles 5a, b in refluxing acetic acid in the presence of sulphuric acid, yielded pyrazolo[3,4-b]pyridines 7a, b. Similarly, pyrazolo[1,5-a]pyrimidines 10a, b and 14a-f were prepared by reaction of enaminone 4 with 5-amino-1H-pyrazoles 8a, b and 12a-f, respectively. The structure of pyrazolo[1,5-a]pyrimidine 10b was determined by X-ray diffraction. The synthesized compounds were tested for their in-vitro antitumor activity against the colon cancer cell line CaCo-2; their cytotoxicity against the normal fibroblast cell line BHK was explored as well. Some of the tested compounds exhibited cell growth inhibitory activity. The significant antitumor activity of compound 14f against the CaCo-2 cell line (IC(50 )= 0.5 microg/mL) was coupled with a lower toxicity against BHK (IC(50 )= 2.3 microg/mL).
Abdel-Aziz
Hatem A
HA
Department of Green Chemistry, National Research Centre, Dokki, Cairo, Egypt. hatem_741@yahoo.com
Saleh
Tamer S
TS
El-Zahabi
Heba S A
HS
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D018938:Caco-2 Cells; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D013844:Thiazoles