Natural dimers of coumarin, chalcones, and resveratrol and the link between structure and pharmacology

• Published in: European journal of medicinal chemistry Vol. 182; p. 111637
• Main Authors: Menezes, José C.J.M.D.S., Diederich, Marc F.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 15.11.2019
• Subjects: Antineoplastic Agents, Phytogenic - chemical synthesis; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Biological Products - chemical synthesis; Biological Products - chemistry; Biological Products - pharmacology; Chalcone; Chalcones - chemical synthesis; Chalcones - chemistry; Chalcones - pharmacology; Coumarin; Coumarins - chemical synthesis; Coumarins - chemistry; Coumarins - pharmacology; Dimer; Dimerization; DNA Topoisomerases - metabolism; Humans; Molecular Structure; Neoplasms - drug therapy; Resveratrol; Resveratrol - chemical synthesis; Resveratrol - chemistry; Resveratrol - pharmacology; Topoisomerase Inhibitors - chemical synthesis; Topoisomerase Inhibitors - chemistry; Topoisomerase Inhibitors - pharmacology; Dimer; Coumarin; Chalcone; Resveratrol
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2019.111637

Natural products like coumarins, chalcones, and resveratrol have inherent biological activity in several models of diseases; therefore, their natural dimeric forms are highlighted in this review and their key structural similarities, isolation and pharmacological significance is discussed. These natural products may be dimerized during their biosynthesis, which proceeds through atom- and energy-sufficient methods involving dimeric enzymes, to provide complex structures from simple compounds. Coumarin-derived dimers features the C–C or C–O–C biaryl, terpene sidechain linkages or by cyclobutane ring and acts as inhibitors of α-glucosidase, and cytochrome p450 while some show anti-inflammatory and anti-viral activities, while chalcone-derived dimers have the 1,3-dihydroxy phenyl (resorcinol) substitution on the periphery of cyclobutane or cyclohexane ring and inhibit topoisomerase, protein tyrosine phosphatase 1B (PTP1B), and cathepsins and others possess anti-cancer, anti-inflammatory, and anti-plasmodial activities. Resveratrol-derived dimers have the resorcinol structure and are formed by oxidative coupling showing antioxidant, neuroprotective, anti-HIV, anti-tyrosinase, and cytotoxic activity. Bioavailability evidence of closely related structural monomers could be applicable to their dimeric forms. Application of bioisosteric principles to such dimeric compounds is also discussed. Overall, these dimeric natural products can provide potent templates for the natural product-based drug discovery against several diseases. To create your abstract, type over the instructions in the template box below. Fonts or abstract dimensions should not be changed or altered. [Display omitted] •Monomeric coumarins, chalcones and resveratrol have inherent biological effect on chronic diseases.•Coumarin derived dimers-inhibition of α-glucosidase, cytochrome 450 enzyme CYP3A4; can function as anti-inflammatory and anti-viral agents.•Chalcone derived dimers- inhibit topoisomerase, protein tyrosine phosphatase 1B (PTP1B), and cathepsins; function as anti-cancer, anti-inflammatory, and anti-plasmodial agents.•Anti-oxidant resveratrol derived dimeric forms- have neuroprotection, anti-HIV, anti-tyrosinase, and cytotoxic activity.•Complexity arising from simple molecules and their biological activity is discussed.