title: Design strategies, structure activity relationship and mechanistic insights for purines as kinase inhibitors.
abstract: Kinases control a diverse set of cellular processes comprising of reversible phosphorylation of proteins. Protein kinases play a pivotal role in human tumor cell proliferation, migration and survival of neoplasia. In the recent past, purine based molecules have emerged as significantly potent kinase inhibitors. In view of their promising potential for the inhibition of kinases, this review article focuses on purines which have progressed as kinase inhibitors during the last five years. A detailed account of the design strategies employed for the synthesis of purine analogs exerting inhibitory effects on diverse kinases has been presented. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the purine analogs for kinase inhibition. The interactions with the amino acid residues responsible for kinase inhibitory potential of purine based molecules have also been discussed. In this assemblage, purine based protein kinase inhibitors patented in the past have also been summarized in the tabular form. This compilation will be of great interest for the researchers working in the area of protein kinase inhibitors.
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
authors.forename: Sahil
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Pharmacy, Rayat-Bahara Group of Institutes, Hoshiarpur, 146001, Punjab, India.
authors.forename: Jagjeet
authors.initials: J
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Ojha
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
authors.forename: Harbinder
authors.initials: H
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
authors.forename: Manpreet
authors.initials: M
authors.lastname: Kaur
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
authors.forename: P M S
authors.initials: PMS
authors.lastname: Bedi
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India. Electronic address: kunal_8855@rediffmail.com.
authors.forename: Kunal
authors.initials: K
authors.lastname: Nepali
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D011687:Purines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D011687:Purines; D014443:Tyrosine; D011494:Protein Kinases
keywords: Cancer; Cell lines; Design strategies; Kinases; Purine; Structure activity relationship