A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboranes, and BODIPY, for the treatment of different human diseases.In addition, we also describe the synthesis, key structure–activity relationship, and associated biological activities, such as antimicrobial, antituberculosis, antitumor, antiparasitic, antiprotozoal, anti-inflammatory, antifolate, antidepressant, antiallergic, anesthetic, and anti-Alzheimer’s agents, as well as proteasome and lipogenic inhibitors. This compilation could be very useful in the exploration of novel boron-derived compounds against different diseases, with promising efficacy and lesser side effects.

Hundreds of billions of commensal microorganisms live in and on our bodies, most of which colonize the gut shortly after birth and stay there for the rest of our lives. In animal models, bidirectional communications between the central nervous system and gut microbiota (Gut–Brain Axis) have been extensively studied, and it is clear that changes in microbiota composition play a vital role in the pathogenesis of various neurodevelopmental and neurodegenerative disorders, such as Autism Spectrum Disorder, Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, anxiety, stress, and so on. The makeup of the microbiome is impacted by a variety of factors, such as genetics, health status, method of delivery, environment, nutrition, and exercise, and the present understanding of the role of gut microbiota and its metabolites in the preservation of brain functioning and the development of the aforementioned neurological illnesses is summarized in this review article. Furthermore, we discuss current breakthroughs in the use of probiotics, prebiotics, and synbiotics to address neurological illnesses. Moreover, we also discussed the role of boron-based diet in memory, boron and microbiome relation, boron as anti-inflammatory agents, and boron in neurodegenerative diseases. In addition, in the coming years, boron reagents will play a significant role to improve dysbiosis and will open new areas for researchers.

Drug delivery systems, which use components at the nanoscale level as diagnostic tools or to release therapeutic drugs to particular target areas in a regulated manner, are a fast-evolving field of science. The active pharmaceutical substance can be released via the drug delivery system to produce the desired therapeutic effect. The poor bioavailability and irregular plasma drug levels of conventional drug delivery systems (tablets, capsules, syrups, etc.) prevent them from achieving sustained delivery. The entire therapy process may be ineffective without a reliable delivery system. To achieve optimal safety and effectiveness, the drug must also be administered at a precision-controlled rate and the targeted spot. The issues with traditional drug delivery are overcome by the development of stimuli-responsive controlled drug release. Over the past decades, regulated drug delivery has evolved considerably, progressing from large- and nanoscale to smart-controlled drug delivery for several diseases. The current review provides an updated overview of recent developments in the field of stimuli-responsive boron-based materials in drug delivery for various diseases. Boron-containing compounds such as boron nitride, boronic acid, and boron dipyrromethene have been developed as a moving field of research in drug delivery. Due to their ability to achieve precise control over drug release through the response to particular stimuli (pH, light, glutathione, glucose or temperature), stimuli-responsive nanoscale drug delivery systems are attracting a lot of attention. The potential of developing their capabilities to a wide range of nanoscale systems, such as nanoparticles, nanosheets/nanospheres, nanotubes, nanocarriers, microneedles, nanocapsules, hydrogel, nanoassembly, etc., is also addressed and examined. This review also provides overall design principles to include stimuli-responsive boron nanomaterial-based drug delivery systems, which might inspire new concepts and applications.

Benzo[c][1,2,5]oxadiazoles and benzo[c][1,2,5]thiadiazoles are recognized to possess potent pharmacological activities including anticancer potential. In continuation of our research endeavors in the development of boron-based heterocycles as potential therapeutic agents, herein we report the design and synthesis of new series of boron-based benzo[c][1,2,5]oxadiazoles and benzo[c][1,2,5]thiadiazoles as anticancer agents targeting tumor hypoxia. A series of seventeen compounds were synthesized in two steps in an efficient manner via substitution reactions followed by subsequent hydrolysis of aryltrifluoroboronate salts into corresponding boronic acid derivatives in the presence of silica. This is the first example to develop boron-based hypoxia agents. The synthesized hybrids were characterized by suitable spectroscopic techniques. The biological studies are currently underway.

Dearomative borylation of coumarins and chromenes via conjugate addition represents a relatively unexplored and challenging task. To address this issue, herein, we report a new and general copper (I) catalyzed dearomative borylation process to synthesize boron-containing oxacycles. In this report, the borylation of coumarins, chromones, and chromenes comprising functional groups, such as esters, nitriles, carbonyls, and amides, has been achieved. In addition, the method generates different classes of potential boron-based retinoids, including the ones with oxadiazole and anthocyanin motifs. The borylated oxacycles can serve as suitable intermediates to generate a library of compounds.

Methionine aminopeptidase 2 (MetAP2) plays an important role in the regulation of protein synthesis and post-translational processing. Preclinical/clinical applications of MetAP2 inhibitors for the treatment of various diseases have been explored because of their antiangiogenic, anticancer, antiobesity, antidiabetic, and immunosuppressive properties. However, the effects of MetAP2 inhibitors on CNS diseases are rarely examined despite the abundant presence of MetAP2 in the brain. Previously, we synthesized a novel boron-containing MetAP2 inhibitor, BL6, and found that it suppressed angiogenesis and adipogenesis yet improved glucose uptake. Here, we studied the anti-inflammatory effects of BL6 in SIM-A9 microglia and in a mouse model of Alzheimer’s disease generated by the intracerebroventricular (icv) injection of streptozotocin (STZ). We found that BL6 reduced proinflammatory molecules, such as nitric oxide, iNOS, IL-1β, and IL-6, together with phospho-Akt and phospho-NF-κB p65, which were elevated in lipopolysaccharide (LPS)-activated microglial SIM-A9 cells. However, the LPS-induced reduction in Arg-1 and CD206 was attenuated by BL6, suggesting that BL6 promotes microglial M1 to M2 polarization. BL6 also decreased glial activation along with a reduction in phospho-tau and an elevation in synaptophysin in the icv-STZ mouse model. Thus, our experiments demonstrate an anti-neuroinflammatory action of BL6, suggesting possible clinical applications of MetAP2 inhibitors for brain disorders in which neuroinflammation is involved.