Imidazole ring is an important five-membered aromatic heterocycle widely present in natural products and synthetic molecules. The unique structural feature of imidazole ring with desirable electron-rich characteristic is beneficial for imidazole derivatives to readily bind with a variety of enzymes and receptors in biological systems through diverse weak interactions, thereby exhibiting broad bioactivities. The related research and developments of imidazole-based medicinal chemistry have become a rapidly developing and increasingly active topic. Particularly, numerous imidazole-based compounds as clinical drugs have been extensively used in the clinic to treat various types of diseases with high therapeutic potency, which have shown the enormous development value. This work systematically gives a comprehensive review in current developments of imidazole-based compounds in the whole range of medicinal chemistry as anticancer, antifungal, antibacterial, antitubercular, anti-inflammatory, antineuropathic, antihypertensive, antihistaminic, antiparasitic, antiobesity, antiviral, and other medicinal agents, together with their potential applications in diagnostics and pathology. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic imidazole-based medicinal drugs, as well as more effective diagnostic agents and pathologic probes.

Comprehensive Review in Current Developments of Imidazole‐Based Medicinal Chemistry

Synthesis and in vitro anti Mycobacterium tuberculosis activity of a series of phthalimide derivatives

Anti-diabetic drugs recent approaches and advancements

The synthesis of new meridianin derivatives is described. The indolic ring system was substituted at the C-4 to C-7 positions either by a bromine atom or by nitro or amino groups. Additionally, an iodine atom or various aryl groups were introduced at the C-5 position of the 2-aminopyrimidine ring. These compounds as well as some of their synthetic intermediates were tested for their kinase inhibitory potencies and for their in vitro antiproliferative activities. We found that this series of compounds is particularly interesting in the development of new inhibitors of DYRK1A and CLK1 kinases. The most effective compounds toward these two kinase families are the 6- and 7-bromo derivatives 30, 33, and 34 that showed more than 45-fold selectivity toward DYRK1A/CLK1 kinases over the other kinases tested. Meridianin derivatives could thus be developed toward potent and selective inhibitors of key RNA splicing regulators and potential therapeutic agents.

Synthesis, protein kinase inhibitory potencies and in vitro antiproliferative activities of meridianin derivatives

Dextran is an exopolysaccharide (EPS) synthesized by lactic acid bacteria (LAB) or their enzymes in the presence of sucrose. Dextran is composed of a linear chain of d-glucoses linked by α-(1→6) bonds, with possible branches of d-glucoses linked by α-(1→4), α-(1→3), or α-(1→2) bonds, which can be low ( 40 kDa). The characteristics of dextran in terms of molecular weight and branches depend on the producing strain, so there is a great variety in its properties. Dextran has commercial interest because its solubility, viscosity, and thermal and rheological properties allow it to be used in food, pharmaceutical, and research areas. The aim of this review article is to compile the latest research (in the past decade) using LAB to synthesize high or low molecular weight dextran. In addition, studies using modified enzymes to produce dextran with specific structural characteristics (molecular weights and branches) are addressed. On the other hand, special attention is paid to LAB extracted from unconventional sources to expose their capacities as dextran producers and their possible application to compete with the only commercial strain (Leuconostoc mesenteroides NRRL B512).

Dextran: Sources, Structures, and Properties

Naturally derived polysaccharides have remained the pharmaceutical excipient of choice for several decades. Natural polysaccharides are preferred by the food and pharma industries for their wide availability, biocompatibility, biodegradability, nontoxicity, environmental friendliness, and cost effectiveness. Despite the inherent challenges posed by undesirable properties, natural polysaccharides have been the focus of research in terms of their applications in evolving technologies in pharmaceutical and biomedical fields. This chapter introduces the reader to the structure and properties of the naturally derived polysaccharides along with its pharmaceutical and biomedical applications.

Natural polysaccharides: Structural features and properties

The emergence and rapid spread of novel coronavirus disease (COVID-19) has posed a serious challenge to global public health in 2020. The speed of this viral spread together with the high mortality rate has caused an unprecedented public health crisis. With no antivirals or vaccines available for the treatment of COVID-19, the medical community is presently exploring repositioning of clinically approved drugs for COVID-19. Chloroquine (CQ) and hydroxychloroquine (HCQ) have emerged as potential candidates for repositioning as anti-COVID-19 therapeutics and have received FDA authorization for compassionate use in COVID-19 patients. On March 28, 2020, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for HCQ in the treatment of COVID-19. However, it was later revoked by the FDA on June 15, 2020, after analyzing the emerging scientific data from ongoing clinical trials. Similarly, the World Health Organization (WHO) also conducted a Solidarity trial of chloroquine, hydroxychloroquine, remdesivir, lopinavir, and ritonavir. However, on May 23, 2020, the executive body of the "Solidarity trial" decided to put a temporary hold on the HCQ trial. On June 17, 2020, the WHO abruptly stopped the Solidarity trial of HCQ. The current review strives to examine the basis of compassionate use of CQ and HCQ for the treatment of COVID-19 in terms of literature evidence, establishing the antiviral efficacy of these drugs against corona and related viruses. Furthermore, the review presents a critical analysis of the clinical trial findings and also provides an insight into the dynamically changing decision on the authorization and withdrawal of HCQ as anti-COVID-19 therapy by the U.S. FDA and the WHO. Ultimately, our study necessitates an evidenced-based treatment protocol to confront the ongoing COVID-19 pandemic and not the mere observational study that mislead the public healthcare system, which paralyzes the entire world.

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The Rise and Fall of Chloroquine/Hydroxychloroquine as Compassionate Therapy of COVID-19

A new approach for PEGylation of dendrimers.

The potential of chewing gum as a drug delivery system together with different formulation principles and methods of assessment are discussed in this article. The release of a drug from chewing gum is dependent upon its water solubility. Water soluble substances are released rapidly and completely from chewing gum and methods are available which retard their release from chewing gum to provide an extended release profile. Slightly water-soluble drugs are released slowly and incompletely from chewing gum and require special formulation techniques to produce a satisfactory release profile. Studies evaluating the potential application of medicated and non-medicated chewing gum in the treatment of local diseases in the oral cavity are described. Specific examples of the use of chewing gum as a delivery system for dental health, smoking cessation and antifungal therapy are cited. Few drugs are suitable candidates for incorporation into chewing gum formulations for the intention of their systemic delivery. Know-how derived from the development and manufacture of already existing medicated and non-medicated chewing gum, supplemented with today's knowledge of the principles of pharmaceutical formulation, constitute the basis for the development of the medicinal chewing gum of tomorrow.

/pdf/chewing-gum-as-a-drug-delivery-system-i6gjo75qwn.pdf

Chewing gum as a drug delivery system

A quantitative structure activity relationship (QSAR) study has been performed on phthalimide analogues based inhibitors of HIV-1 integrase to understand the structural features influencing the affinity of these inhibitors towards the enzyme. The compounds in the selected series were characterized by molecular descriptors calculated using the QSAR software Dragon and molecular modeling software ChemOffice 2001. QSAR models were derived by stepwise multiple regression analysis employing the method of least squares. The best QSAR model describing the HIV-1 integrase inhibitory activity of phthalimide analogues was selected on the basis of statistical significance and predictive ability as gauged by cross-validation procedure and external test-set method. The generated QSAR models revealed that increased HIV-1 inhibitory potency of tricyclic phthalimide derivatives could be achieved by increasing the overall lipophilicity of the molecules and by incorporating halogen substituents in the benzylic aromatic ring attached to the phthalimido nitrogen atom. Additionally, the model also suggests that the increase in the molecular flexibility by incorporation of rotatable bonds is conducive for HIV-1 inhibitory activity of phthalimide derivatives whereas increase in molecular branching appears to be detrimental to the activity.

C. Karthikeyan

Papers

Natural polysaccharides: Structural features and properties

The Rise and Fall of Chloroquine/Hydroxychloroquine as Compassionate Therapy of COVID-19

A new approach for PEGylation of dendrimers.

Chewing gum as a drug delivery system

QSAR analysis of some phthalimide analogues based inhibitors of HIV-1 integrase