Mini Reviews in Medicinal Chemistry - Volume 19, Issue 9, 2019

In this review, specific therapeutic and medicinal advantages including antiviral, antibacterial, antifungal and antitumor, strategies for drug designing, structure-activity relationship, advances in the syntheses of azo and hippuric acid derivatives of more than 50 compounds have been discussed since 2009-2018. It is found that phenyl-diazenyl azo derivatives and pyridinyl substituted hippuric acid derivatives showed promising antiretroviral potential. The incorporation of azo functionality to the respective quinolones and coumarin moieties and the insertion of thiocarbazone to hippuric acid displayed immense antibacterial activities. While, azo and hippuric acid derivatives of triazole and phenyl species gave maximum fungicidal as well as cytotoxic activities.

Although it is generally accepted that selenium (Se) is important for life, it is not well known which forms of organic and/or inorganic Se compound are the most biologically active. In nature Se exists mostly in two forms, namely as selenite with fourvalent and selenate with sixvalent cations, from which all other inorganic and organic species are derived. Despite a small difference in their electronic structure, these two inorganic parent compounds differ significantly in their redox properties. Hence, only selenite can act as an oxidant, particularly in the reaction with free and/or protein- bound sulhydryl (SH) groups. For example, selenite was shown to inhibit the hydroxyl radicalinduced reduction and scrambled reoxidation of disulfides in human fibrinogen thus preventing the formation of highly hydrophobic polymer, termed parafibrin. Such a polymer, when deposited within peripheral and/or cerebral circulation, may cause irreversible damage resulting in the development of cardiovascular, neurological and other degenerative diseases. In addition, parafibrin deposited around tumor cells produces a protease-resistant coat protecting them against immune recognition and elimination. On the other hand, parafibrin generated by Ebola’s protein disulfide isomerase can form a hydrophobic ‘spike’ that facilitates virus attachment and entry to the host cell. In view of these specific properties of selenite this compound is a potential candidate as an inexpensive and readily available food supplement in the prevention and/or treatment of cardiovascular, neoplastic, neurological and infectious diseases.

Azaindoles have been accepted as important structures having various biological activities in medicinal chemistry in novel drug discovery. Various azaindole derivatives have been used commercially and newer analogues are synthesized continuously. As in literature, azaindole is a very potent moiety, its derivatives displayed a number of biological activities such as kinase inhibitors, cytotoxic agents, anti-angiogenic activity, CRTh2 receptor antagonists, melanin agonists, nicotine agonists, effectiveness in alzheimer disease, cytokinin analogs, Orai inhibitors in asthma and chemokine receptor- 2 (CCR2) antagonists. This review consists of biological activities of various azaindole analogs, reported so far, and their structure activity relations, along with future perspectives in this field.

Derived from chitin, chitosan is a natural polycationic linear polysaccharide being the second most abundant polymer next to cellulose. The main obstacle in the wide use of chitosan is its almost complete lack of solubility in water and alkaline solutions. To break this obstacle, the structure of chitosan is subjected to modification, improving its physic-chemical properties and facilitating application as components of composites or hydrogels. Derivatives of chitosan are biomaterials useful for different purposes because of their lack of toxicity, low allergenicity, biocompatibility and biodegradability. This review presents the methods of chemical modifications of chitosan which allow to obtain tailor- made properties required for a variety of biomedical applications. Selected pharmaceutical and biomedical applications of chitosan derivatives are also highlighted. Possibility to manage waste from arthropod and crab processing is also emphasized.

Marine bis-indole alkaloids comprise a large and increasingly growing class of secondary metabolites, and continue to deliver a great variety of structural templates for diverse biological targets. The alkaloids derived from marine resources play a crucial role in medicinal chemistry and as chemical agents. In particular, bis-indole alkaloid caulerpin which has been isolated from marine green algae Caulerpa and a red algae Chondria armata at various places around the world, was tested for several therapeutic potentials such as anti-diabetic, antinociceptive, anti-inflammatory, anti-tumor, anti- larvicidal, anti-herpes, anti-tubercular, anti-microbial and immunostimulating activities as well as a means of other chemical agents. Herein, we summarized the discovery and isolation of caulerpin, and its potential medicinal and chemical applications in chronological order with various aspects. Additionally, synthesis of caulerpin and its functional analogues have also been reviewed.

The development of drugs possessing anti-diabetic activities is a long pursued goal in drug discovery. It has been shown that deregulated insulin mediated signaling, oxidative stress, obesity, and β-cell dysfunction are the main factors responsible for the disease. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can effectively treat diabetes by targeting different pathways has re-bloomed. Current anti-diabetic therapy is based on synthetic drugs that very often have side effects. For this reason, there is an instantaneous need to develop or search new alternatives. Recently, more attention is being paid to the study of natural products. Their huge advantage is that they can be ingested in everyday diet. Here, we discuss various causes, putative targets, and treatment strategies, mechanistic aspects as well as structural features with a particular focus on naturally occurring flavonoids as promising starting points for anti-diabetic led development.