Boronic Acids and Their Derivatives in Medicinal Chemistry: Synthesis and Biological Applications

Abstract

Boron containing compounds have not been widely studied in Medicinal Chemistry, mainly due to the idea that this group could confer some toxicity. Nowadays, this concept has been demystified and, especially after the discovery of the drug bortezomib, the interest for these compounds, mainly boronic acids, has been growing. In this review, several activities of boronic acids, such as anticancer, antibacterial, antiviral activity, and even their application as sensors and delivery systems are addressed. The synthetic processes used to obtain these active compounds are also referred. Noteworthy, the molecular modification by the introduction of boronic acid group to bioactive molecules has shown to modify selectivity, physicochemical, and pharmacokinetic characteristics, with the improvement of the already existing activities. Besides, the preparation of compounds with this chemical group is relatively simple and well known. Taking into consideration these findings, this review reinforces the relevance of extending the studies with boronic acids in Medicinal Chemistry, in order to obtain new promising drugs shortly.

Saturated Boronic Acids, Boronates, and Trifluoroborates: An Update on Their Synthetic and Medicinal Chemistry

“…Although boric acid (H 3 BO 3 ) has been used as a mild antiseptic and eye wash agent since the 19th century, and boron compounds have important biological and physiological functions, [9] as well as a particular role in prebiotic chemistry, [10] the widespread use of organoboron compounds in drug design started only a few decades ago. [2,[11][12][13][14][15][16][17][18] The main reason behind this can be related to the unjustified assumption that organoboron compounds might be unstable and/or toxic in living organisms. Nevertheless, boric acid (which is the major metabolite of organoboron compounds), is as toxic as sodium chloride (oral LD 50 values in rats are 2660 and 3000 mg/kg for H 3 BO 3 and NaCl, respectively).…”

“…Recently, αand β-aminoboronic acids and their derivatives were surveyed comprehensively; [21][22][23] a number of more general reviews on organoboron compounds in medicinal chemistry were also published. [2,[11][12][13][14][15][16][17][18] Therefore, we shall limit further discussion by overview of recent approaches to the synthesis of enantiopure α-aminoboronic acids or their derivatives.…”

Organoboron Compounds: Effective Antibacterial and Antiparasitic Agents

“…This review will focus on the particular type of bioactivity of organoboron compounds covering the medicinal applications in infectious disease caused by protozoa , fungi and helminths , describing progress in drug development, cytotoxicity and the proposed mechanisms of action. Other organoboron compound-based antibacterial or antiviral drugs have been reviewed elsewhere [ 21 , 22 ]. Thus, the review covers four areas of therapeutic applications of organoboron compounds: tuberculosis and antifungal activity, malaria, neglected tropical diseases and cryptosporidiosis and toxoplasmosis.…”

Merging the Versatile Functionalities of Boronic Acid with Peptides

“…Given the considerable potential of boronic acids, it is vital to review the recent advances of boronic acid as a versatile functional group. Reviews in the past decade have focused on the wide applications of boronic acid-based small molecule drugs [ 1 , 2 , 4 , 6 , 20 , 21 ], molecular recognition and sensing [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ], polymers [ 3 ], protein modifications [ 17 ], bioconjugation [ 18 ], and dynamic click chemistry [ 30 ]. Herein, we prioritize the integration between boronic acid and peptides, an important but largely overlooked perspective.…”