RESUMO
Cancer is a major cause of deaths across the globe due to chemoresistance and lack of selective chemotherapy. Pyrido[2,3-d]pyrimidine is an emerging scaffold in medicinal chemistry having a broad spectrum of activities, including antitumor, antibacterial, CNS depressive, anticonvulsant, and antipyretic activities. In this study, we have covered different cancer targets, including tyrosine kinase, extracellular regulated protein kinases - ABL kinase, phosphatidylinositol-3 kinase, mammalian target of rapamycin, p38 mitogen-activated protein kinases, BCR-ABL, dihydrofolate reductase, cyclin-dependent kinase, phosphodiesterase, KRAS and fibroblast growth factor receptors, their signaling pathways, mechanism of action and structure-activity relationship of pyrido[2,3-d]pyrimidine derivatives as inhibitors of the above-mentioned targets. This review will represent the complete medicinal and pharmacological profile of pyrido[2,3-d]pyrimidines as anticancer agents, and will help scientists to design new selective, effective and safe anticancer agents.
RESUMO
Collagen is the most important structural protein and also the main component of the extra-cellular matrix (ECM). It plays a role in tumor progression. Collagen can be regulated by altering its biosynthesis pathway through various signaling pathways, receptors, and genes. The activity of cancer cells can also be regulated by other ECM components like metalloproteinases, hyaluronic acid, fibronectin, and so on. Hypoxia is also one of the conditions that lead to cancer progression by stimulating the expression of procollagen lysine as a collagen crosslinker, which increases the size of collagen fibres promoting cancer spread. The collagen content in cancerous cells leads to resistance to chemotherapy. So, to reduce this resistance, some collagen-regulating therapies are introduced, including inhibiting its biosynthesis, disturbing cancer cell signaling pathway, mediating ECM components, and directly utilizing collagenase. This study is an effort to compile the strategies reported to control the collagen level and different collagen inhibitors reported so far. More research is needed in this area. Growing understanding of collagen's structural features and its role in cancer progression will aid in the advancement of newer chemotherapies.
