title: Novel pyrazolo[3,4-d]pyrimidines as dual Src-Abl inhibitors active against mutant form of Abl and the leukemia K-562 cell line.
abstract: Some novel 6-substituted pyrazolo[3,4-d]pyrimidines 4, 5, 6a-d, 7a-c, 8 and pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidines 9a-c, 10a-c, 11, 12a,b, 13a-c and 14 were synthesized and characterized by spectral and elemental analyses. They were screened for their biological activity in vitro against Abl and Src kinases. Compounds 7a and 7b revealed the highest activity against both wild and mutant Abl kinases as well as the Src kinase and the leukemia K-562 cell line. They can be considered as new hits for further structural optimization to obtain better activity.
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, El-kasr Elaini Street, Cairo 11562, Egypt.
authors.forename: Samir M
authors.initials: SM
authors.lastname: El-Moghazy
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, El-kasr Elaini Street, Cairo 11562, Egypt. Electronic address: rihamfgeorge@yahoo.com.
authors.forename: Riham F
authors.initials: RF
authors.lastname: George
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, El-kasr Elaini Street, Cairo 11562, Egypt.
authors.forename: Essam Eldin A
authors.initials: EEA
authors.lastname: Osman
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nahda University, Beni Suef 62511, Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Elbatrawy
authors.affiliation: Istituto di Genetica Molecolare, IGM-CNR, Via Abbiategrasso 207, I-27100 Pavia, Italy.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Kissova
authors.affiliation: Istituto di Genetica Molecolare, IGM-CNR, Via Abbiategrasso 207, I-27100 Pavia, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Colombo
authors.affiliation: Istituto di Genetica Molecolare, IGM-CNR, Via Abbiategrasso 207, I-27100 Pavia, Italy.
authors.forename: Emmanuele
authors.initials: E
authors.lastname: Crespan
authors.affiliation: Istituto di Genetica Molecolare, IGM-CNR, Via Abbiategrasso 207, I-27100 Pavia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors* / Q000235:genetics; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C014175:pyrazolo(3,4-d)pyrimidine; D016315:Proto-Oncogene Proteins c-abl; D019061:src-Family Kinases
keywords: Abl inhibition; K-562 cell line; Molecular modeling; Pyrazolo[3,4-d]pyrimidines; Src inhibition