Cancer is now widely recognized as a global problem that unfortunately lacks a global solution. The latest United Nations high-level meeting on noncommunicable diseases (NCDs) exemplified this conundrum.¹ Despite global commitment to reducing the risk of and disability from NCDs, including cancer, implementation of known solutions is inadequate to reach the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases^2,3 (25% reduction in premature mortality from NCDs by 2025) and the third Sustainable Development Goal (by 2030 reduce by one-third premature mortality from NCDs through prevention and treatment, and promote mental health and well-being).⁴ To reduce cancer burden, identifying the scope of the problem and mapping out implementation of solutions is best done in National Cancer Control Plans (NCCPs). However, a recent review showed that only 29% of low-income countries had a NCCP, and even if NCCPs existed, cost, financing, monitoring, and expansion of information systems was often inadequate. Many highly effective prevention and treatment strategies exist for cancer. However, they are often very specific (eg, vaccination for human papillomavirus and hepatitis B virus for prevention of cervical and liver cancer, or tyrosine kinase inhibitors for cancers with targetable mutations). Effective NCCPs therefore require detailed knowledge about the local burden of cancer and associated risk factors. We herein present results from the Global Burden of Disease (GBD) 2017 study describing cancer incidence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 195 countries from 1990 through 2017, which can inform cancer control through policy, resource allocation, and health system planning.

α-Glucosidase inhibitors are described as the most effective in reducing post-prandial hyperglycaemia (PPHG) from all available anti-diabetic drugs used in the management of type 2 diabetes mellitus. As flavonoids are promising modulators of this enzyme’s activity, a panel of 44 flavonoids, organised in five groups, was screened for their inhibitory activity of α-glucosidase, based on in vitro structure–activity relationship studies. Inhibitory kinetic analysis and molecular docking calculations were also applied for selected compounds. A flavonoid with two catechol groups in A- and B-rings, together with a 3-OH group at C-ring, was the most active, presenting an IC₅₀ much lower than the one found for the most widely prescribed α-glucosidase inhibitor, acarbose. The present work suggests that several of the studied flavonoids have the potential to be used as alternatives for the regulation of PPHG. Graphical Abstract

Type 2 diabetes (T2D) is one of the most prevalent metabolic diseases worldwide and is characterized by increased postprandial hyperglycemia (PPHG). α-Amylase and α-glucosidase inhibitors have been shown to slow the release of glucose from starch and oligosaccharides, resulting in a delay of glucose absorption and a reduction in postprandial blood glucose levels. Since current α-glucosidase inhibitors used in the management of T2D, such as acarbose, have been associated to strong gastrointestinal side effects, the search for novel and safer drugs is considered a hot topic of research. Flavonoids are phenolic compounds widely distributed in the Plant Kingdom and important components of the human diet. These compounds have shown promising antidiabetic activities, including the inhibition of α-amylase and α-glucosidase. The aim of this review is to provide an overview on the scientific literature concerning the structure-activity relationship of flavonoids in inhibiting α-amylase and α-glucosidase, including their type of inhibition and experimental procedures applied. For this purpose, a total of 500 compounds is covered in this review. Available data may be considered of high value for the design and development of novel flavonoid derivatives with effective and potent inhibitory activity against those carbohydrate-hydrolyzing enzymes, to be possibly used as safer alternatives for the regulation of PPHG in T2D.

α-Amylase has been considered an important therapeutic target for the management of type 2 diabetes mellitus (T2DM), decreasing postprandial hyperglycaemia (PPHG). In the present work, a panel of 40 structurally related flavonoids was tested, concerning their ability to inhibit α-amylase activity, using a microanalysis screening system, an inhibitory kinetic analysis and molecular docking calculations. From the obtained results, it was possible to observe that the flavone with a -Cl ion at 3-position of C-ring, an –OH group at 3′- and 4′- positions of B-ring and at 5- and 7- positions of A-ring and the C2 = C3 double bond, was the most active tested flavonoid, through competitive inhibition. In conclusion, some of the tested flavonoids have shown promising inhibition of α-amylase and may be considered as possible alternatives to the modulation of T2DM. Graphical Abstract