Mini Reviews in Medicinal Chemistry - Volume 18, Issue 14, 2018

Cocrystallization is a technique for modifying the physicochemical and pharmacokinetic properties of an active pharmaceutical ingredient (API) embodying the concept of supramolecular synthon. Most of the examples cited in the literature are of cocrystals formed between an API and a coformer chosen from the generally recognized as safe (GRAS) substance list; however few examples exist where a cocrystal consists of two or more APIs. These cocrystals are commonly known as multi API, multi-drug or drug- drug cocrystals. The formation of such cocrystals is feasible by virtue of non covalent interactions between the APIs, which help them in retaining their activity. In addition, drugdrug cocrystals also offer potential solution to the limitations such as solubility, stability differences and chemical interaction between the APIs which is often faced during the traditional combination therapy. Cocrystallization of two or more APIs can be employed for delivery of combination drugs for the better and efficacious management of many complex disorders where existing monotherapies do not furnish the desired therapeutic effect. This review on the existing drug-drug cocrystals is to gain an insight for better designing of multi API cocrystals with improved physicochemical and pharmacokinetic profile and its application in multiple target therapy.

In the past decades, many efforts were undertaken to develop ligands for the adenosine receptors, with the purpose to individuate agonists and antagonists affinity and selectivity for each subtypes, namely A1, A2A, A2B, and A3. These intense studies allowed a deeper knowledge of the nature and, moreover, of the pathophysiological roles of all the adenosine receptor subtypes. In particular, the involvement of the A2A adenosine receptor subtype in some physiological mechanisms in the brain, that could be related to important diseases such as the Parkinson's disease, encouraged the research in this field. Particular attention was given to the antagonists endowed with high affinity and selectivity since they could have a real employment in the treatment of Parkinson's disease, and some compounds, such as istradefylline, preladenant and tozadenant, are already studied in clinical trials. Actually, the role of A2A antagonists in Parkinson's disease is becoming contradictory due to contrasting results in the last studies, but, at the same time, new possible employments are emerging for this class of antagonists in cancer pathologies as much interesting to legitimate further efforts in the research of A2A ligands.

The free radical nitric oxide (NO) is considered one of the most versatile endogenous molecules and is a crucial signalling molecule in numerous biochemistry pathways of the human body. NO is directly related to pathological processes and plays an important role in many different and interrelated physiological processes. In some cases, a depletion of NO or an attenuation of its effector system could exist as in hypertension, angina and impotence; in others, an overproduction of NO may be a major cause of damage, as in circulatory shock, sepsis, neurodegenerative disorders and inflammatory responses. By using certain functional groups present in molecules that already have potential therapeutic value, hybrid compounds, by means of inclusion of NO-donors (e.g., ester nitrates and nitrites, S-nitrosothiols, metal complexes, furoxans, oxadiazoles, diazeniumdiolates and NO nanoparticles), can be developed that have a NO release benefit along with maintaining the activity of the native drug. The objective of the design of NO-donor hybrid compounds is to achieve a balance between the release of therapeutic amounts of NO, especially in the site of action, and maintaining the native drug activity. This review explores some of the most promising recent advances in NO-donor drug development and addresses the challenges associated with NO as a therapeutic agent.

As a therapeutic group, non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used, prescribed and over the counter (OTC) medications for the treatment of inflammatory diseases, but suffering from several undesired side effects, the most important being ulcerogenicity, mucosal hemorrhage and gastritis. Most of the NSAID moieties are chemically composed of carboxylic functional groups and this could be one of the reasons for the damage to the mucosal lining. The prodrug designing is one of the several strategies used to overcome this drawback. Hence, in the last decade, the design and the synthesis of prodrugs of NSAIDs have been explored and given much attention by medicinal chemists. The rationale behind the prodrug concept is to achieve temporary blockade of the free carboxylic group present in the NSAIDs till their systemic absorption. This review is aimed to highlight and provide important information on NSAID prodrugs that have been designed and reported to be safe and more effective. This review will also focus on NSAID prodrugs that have been designed for improving therapeutic i.e. anti-inflammatory action as well as improving drug delivery at the target site. The most common derivatives of carboxylic NSAIDs that are discussed here belong to the chemical classes of esters, amides, anhydrides, acetals and the other derivatives with completely masked carboxylic groups. The successful prodrugs were listed and their molecular structures were also demonstrated here. The present review covers the recent updates present in literature and will surely provide a greater insight into the designing of safer NSAIDs in the future.

The plant Alpinia officinarum of the ginger family originated in China and is used throughout South and South-East Asian countries to flavor food and as a traditional medicine to treat a variety of diseases. This review summarizes the biological, pharmacological and phytochemical properties of extracts and subsequently isolated compounds from A. officinarum. In vitro and in vivo studies of both extracts and pure compounds indicate a wide variety of potent bioactivities including antiinflammatory, antibacterial, antioxidant, antiobesity, anticancer, enzyme inhibitory and remarkable antiviral properties. The latter is particularly promising in the face of emerging, virulent respiratory diseases in Asia and the Middle East.

Background: The ultrasound assisted synthesis and anti-bacterial evaluation of a series of compounds based on 1,2-disubstituted benzimidazole framework is reported here. The approach leading to the synthesis of these compounds involved the Cu-catalyzed coupling-cyclization of N-substituted 2-iodoanilines with benzamide derivatives in the presence of 2-aminoethanol as a ligand. Conclusion: A number of compounds were prepared using this methodology in acceptable yield. Two of these compounds showed promising antibacterial activities when tested against both Gram-positive and Gram-negative bacterial strains.