Natural products to drugs: natural product derived compounds in clinical trials

The methyl group is one of the most commonly occurring carbon fragments in small-molecule drugs. This simplest alkyl fragment appears in more than 67 % of the top-selling drugs of 2011 and can modulate both the biological and physical properties of a molecule. This Review focuses on so-called magic methyl effects on binding potency, where the seemingly mundane change of CH to CMe improves the IC50  value of a drug candidate more than 100-fold. This discussion is followed by a survey of recent advances in synthetic chemistry that allow the direct methylation of C(sp(2) )H and C(sp(3) )H bonds. It is our hope that the relevance of the meager methyl group to drug discovery as presented herein will inspire reports on new CH methylation reactions.

Profound methyl effects in drug discovery and a call for new C-H methylation reactions.

α- and β-Glucosidase inhibitors: chemical structure and biological activity

In the current study, three different types of cheese, cheddar, feta, and Roquefort, were screened to determine the variations in phenolic-linked antioxidant activity and the potential to inhibit key enzymes relevant to type 2 diabetes and related hypertension. The cheese samples were assayed for total phenolic content, related antioxidant activity, and inhibition of α-glucosidase, pancreatic α-amylase inhibitory activity, and the angiotensin-converting enzyme (ACE)-I inhibitory activity. The three fungal-enriched Roquefort cheese samples had the highest total phenolic content. The phenolic content in the herb cheese was slightly but not significantly higher compared to plain cheese. Roquefort cheese samples had the highest antioxidant-linked DPPH (free radical) scavenging activity and as expected DPPH radical scavenging activity was higher in the herb cheese compared to plain cheese. All samples had some α-glucosidase and α-amylase inhibitory activities, with cranberry-enriched cheese having the highest activities. However, no correlation to soluble phenolic content was observed. All the cheese samples had very high anti-ACE-I inhibitory activity, indicating no correlation to phenolic content and activity was even high in 10× diluted samples. The highest ACE-I inhibitory activity was observed in plain and herb-enriched cheddar cheese as well as cranberry-enriched cheese. These studies indicate that cranberry-enriched cheese had the best potential for inhibition of α-glucosidase and α-amylase relevant for type 2 diabetes management, whereas any cheese product had potential for ACE-I inhibition linked to hypertension management, indicating likely the role of other factors such as peptides from cheese fermentation. Industrial relevance This research is focused on screening of different types of commercial plain, herbal, fruit, and fungal-enriched to provide a strong biochemical rationale for further design of functional cheese products for anti-type 2 diabetic and relevant hypertension management. A better understanding of these functional attributes provides a strong biochemical rationale for design in vivo and clinical studies from which right design of functional food can be established.

Inhibitory potential of herb, fruit, and fungal-enriched cheese against key enzymes linked to type 2 diabetes and hypertension

Natural product and natural product derived drugs in clinical trials

Molecular design, synthesis, and hypoglycemic and hypolipidemic activities of novel pyrimidine derivatives having thiazolidinedione.

Synthesis and biological activity of novel substituted pyridines and purines containing 2,4-thiazolidinedione.

Design and synthesis of highly potent fumagillin analogues from homology modeling for a human MetAP-2

Structure-based virtual screening of novel tubulin inhibitors and their characterization as anti-mitotic agents

Total synthesis and antiangiogenic activity of cyclopentane analogues of fumagillol

Soon Kil Ahn

Papers

Molecular design, synthesis, and hypoglycemic and hypolipidemic activities of novel pyrimidine derivatives having thiazolidinedione.

Synthesis and biological activity of novel substituted pyridines and purines containing 2,4-thiazolidinedione.

Design and synthesis of highly potent fumagillin analogues from homology modeling for a human MetAP-2

Structure-based virtual screening of novel tubulin inhibitors and their characterization as anti-mitotic agents

Total synthesis and antiangiogenic activity of cyclopentane analogues of fumagillol