Pyrimidine and fused pyrimidine derivatives as promising protein kinase inhibitors for cancer treatment
- PDF / 2,086,555 Bytes
- 19 Pages / 595.276 x 790.866 pts Page_size
- 75 Downloads / 204 Views
Medicinal Chemistry Research https://doi.org/10.1007/s00044-020-02656-8
REVIEW ARTICLE
Pyrimidine and fused pyrimidine derivatives as promising protein kinase inhibitors for cancer treatment Khaled R. A. Abdellatif1,2 Rania B. Bakr1 ●
1234567890();,:
1234567890();,:
Received: 9 July 2020 / Accepted: 17 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Pyrimidine ring and its fused derivatives including pyrazolo[3,4-d]pyrimidine, pyrido[2,3-d]pyrimidine, quinazoline, and furo[2,3-d]pyrimidine compounds had received much interest due to their diverse biological potential, in addition fused pyrimidine are considered as bioisosteres with purines and consequently many pyrimidine and fused pyrimidine derivatives as pyrazolo[3,4-d]pyrimidine, pyrido[2,3-d]pyrimidine, quinazoline, and furo[2,3-d]pyrimidine possessed promising anticancer activity. These pyrimidine derivatives exerted their anticancer potential through different action mechanisms; one of these mechanisms is inhibiting protein kinases that are considered as essential enzymes for controlling cell growth, differentiation, migration, and metabolism. The present review sheds the light on the anticancer significance of some privileged pyrimidine and fused pyrimidine derivatives via selective inhibition of protein kinases, revealing structure-activity relationships and some synthetic pathways used for constructing these scaffolds in an attempt to assist medicinal chemists to construct novel pyrimidines with higher selectivity as anticancer agents. Keywords Anticancer agents Erlotinib Pyrazolo[3,4-d]pyrimidines Bioisosteres Pyrimidine scaffold ●
●
Introduction Cancer is still one of the most fatal diseases, affecting nearly 7 million persons per year all over the world. It is characterized by loss of cell growth control causing a cellular mass called cancer [1–6]. However, death is most often accompanies cancer because of metastasis which is responsible for spreading cancer to another part in the body to establish secondary cancerous growths [7–12]. It was found that strategies for cancer treatment such as surgery and radiation cannot control the spread of tumor; so many scientific trials to treat cancer had been depending on conventional chemotherapy [13–16]. Unfortunately, the conventional chemotherapy did not differentiate between the normal human cells and affected cells, causing many drawbacks [17, 18]. Consequently, to circumvent these
* Khaled R. A. Abdellatif [email protected] 1
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt
2
Pharmaceutical Sciences Department, Ibn Sina National College for Medical Studies, Jeddah 21418, Kingdom of Saudi Arabia
●
●
drawbacks a new strategy for cancer treatment compromising the use of selective tumor drugs called molecular targeted therapies which inhibits certain receptors and signaling pathways which stimulate tumor cell growth had been developed [19–22]. Protein kinases (PKs) are enzymes tha
Data Loading...
