Recent Advances in the Use of the Dimerization Strategy as a Means to Increase the Biological Potential of Natural or Synthetic Molecules

Abstract

The design of C2-symmetric biologically active molecules is a subject of interest to the scientific community. It provides the possibility of discovering medicine with higher biological potential than the parent drugs. Such molecules are generally produced by classic chemistry, considering the shortness of reaction sequence and the efficacy for each step. This review describes and analyzes recent advances in the field and emphasizes selected C2-symmetric molecules (or axial symmetric molecules) made during the last 10 years. However, the description of the dimers is contextualized by prior work allowing its development, and they are categorized by their structure and/or by their properties. Hence, this review presents dimers composed of steroids, sugars, and nucleosides; known and synthetic anticancer agents; polyphenol compounds; terpenes, known and synthetic antibacterial agents; and natural products. A special focus on the anticancer potential of the dimers transpires throughout the review, notwithstanding their structure and/or primary biological properties.

Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets

“…This specificity is likely to be lost with the trimeric agent 21 , where the potency is in double digit micromolar region as well. Our data are similar to what has been seen in investigations of linker lengths in dimeric agents targeting G protein-coupled receptors [ 39 ], estrogen receptors [ 40 ], proteolysis targeting chimeras [ 39 ], among others [ 41 ].…”

Anti-Cancer and Electrochemical Properties of Thiogenistein—New Biologically Active Compound

“…In a preliminary in-vitro study, it was recognized that TGE has a higher cytotoxic activity towards DU145 prostate cancer cells and is safer for normal prostate epithelial cells (PNT2) than genistein (GE) itself. Moreover, the formation of TGE trimers upon oxidation deduced from the present study may enhance the biological response than the parent drug due to the synergizing of this response [50][51][52]. Most often, dimeric/trimeric drugs are not released (or cleaved) within the cell, so they can act as a completely new molecular unit inside the targeted cells [52].…”

“…Moreover, the formation of TGE trimers upon oxidation deduced from the present study may enhance the biological response than the parent drug due to the synergizing of this response [50][51][52]. Most often, dimeric/trimeric drugs are not released (or cleaved) within the cell, so they can act as a completely new molecular unit inside the targeted cells [52]. The TGE monolayer firmly bound to the Au surface described in the present work may contribute to the design and development of the carriers of medicines in nanotechnology of biological applications.…”

Discovery of Dimeric Arylsulfonamides as Potent ADAM8 Inhibitors

“…Dimerization as a strategy to increase the biological activity of natural and synthetic molecules has been largely pursued in the last several years. 12 In this context, the binding of a bifunctional ligand to the catalytic sites of an ADAM8 active homodimer on the tumor cell membrane could efficiently reduce ADAM8-mediated tumor growth and invasion to the surrounding tissues. Considering the high homology between the catalytic sites of ADAM8 and ADAM17, 13 we hypothesized that a bifunctional molecule deriving from the symmetric dimerization of a potent ADAM17 inhibitor could have high activity on ADAM8.…”

“…Dimerization as a strategy to increase the biological activity of natural and synthetic molecules has been largely pursued in the last several years . In this context, the binding of a bifunctional ligand to the catalytic sites of an ADAM8 active homodimer on the tumor cell membrane could efficiently reduce ADAM8-mediated tumor growth and invasion to the surrounding tissues.…”