Mini Reviews in Medicinal Chemistry - Volume 20, Issue 7, 2020

In the last 2-3 decades, the broad research in the application of benzimidazole derivatives made it important for mankind. Many scientists have worked on benzimidazole derivatives and they found that this compound has a diverse role in the field of medicinal chemistry. Few benzimidazole derivatives are currently in the market as a drug candidate against various diseases. Moreover, the benzimidazole derivatives exhibit pharmacological activities such as anti-tuberculosis, anti-malarial, antihistamine, antimicrobial, antiviral, antidiabetic, anticancer, anti-fungal, anti-inflammatory, analgesic, anti-HIV, etc. In this review, we have summarized various derivatives of benzimidazole which have been prepared by many researchers to understand the chemistry as well as diverse pharmacological activities. These findings may lead the scientists who are working in the field of medicinal chemistry to the development of benzimidazole based drug candidates in the future.

Natural plant bioactive compounds (PBC) have recently been explored as feed additives to improve productivity, health and welfare of poultry following ban or restriction of in-feed antibiotic use. Depending upon the types of PBC, they possess antimicrobial, digestive enzyme secretion stimulation, antioxidant and many pharmacological properties, which are responsible for beneficial effects in poultry production. Moreover, they may also improve the intestinal barrier function and nutrient transport. In this review, the effects of different PBC on the barrier function, permeability of intestinal epithelia and their mechanism of actions are discussed, focusing on poultry feeding. Dietary PBC may regulate intestinal barrier function through several molecular mechanisms by interacting with different metabolic cascades and cellular transcription signals, which may then modulate expressions of genes and their proteins in the tight junction (e.g., claudins, occludin and junctional adhesion molecules), adherens junction (e.g., E-cadherin), other intercellular junctional proteins (e.g., zonula occludens and catenins), and regulatory proteins (e.g., kinases). Interactive effects of PBC on immunomodulation via expressions of several cytokines, chemokines, complement components, pattern recognition receptors and their transcription factors and cellular immune system, and alteration of mucin gene expressions and goblet cell abundances in the intestine may change barrier functions. The effects of PBC are not consistent among the studies depending upon the type and dose of PBC, physiological conditions and parts of the intestine in chickens. An effective concentration in diets and specific molecular mechanisms of PBC need to be elucidated to understand intestinal barrier functionality in a better way in poultry feeding.

Nonalcoholic Fatty Liver Disease (NAFLD) includes a variety of changes including nonalcoholic fatty liver, cirrhosis and Hepatocellular Carcinoma (HCC), which are associated with metabolic disorders and cardiovascular diseases. The pathogenesis of NAFLD is complex and multifactorial. Many studies have shown that estrogen has a protective effect on premenopausal women with metabolic disorders and non-alcoholic fatty liver disease. Estrogen supplements may, at least in theory, prevent the development and progression of NAFLD. Phytoestrogen is extracted from plants, especially legumes, whose molecular structure and biological activity are similar to those of mammals estrogen, therefore it could replace the role of estrogen and prevent the occurrence of adverse reactions to estrogen. In this article, we review the published literature related to phytoestrogens and NAFLD as well as suggest the possible mechanisms that may underlie the association between phytoestrogens and NAFLD.

The resistance among various microbial species (infectious agents) to different antimicrobial drugs has emerged as a cause of serious public health problem all over the world. In this sense, natural products have been a rich source of compounds for drug discovery with antibiotic activity. Macrolactins are amazing structures which have antibiotic activity against some clinically relevant pathogens. In addition, they have anti-inflammatory, antifungal, antimicrobial, and antitumor activities. They are macrolides containing 24-membered lactone ring with some differences in their chemical structures. The synthesis of these compounds is a difficult task which has attracted attention of researchers; however few syntheses have been reported. In this review, the isolation of all reported macrolactins, their syntheses and biological activities are revisited.

The chemical modification of natural products has been a major method in the discovery and synthesis of new macrolide antibiotics (MA) to treat a variety of infectious diseases. However, a lot of MA obtained in the above methods are no longer effective, because the bacteria quickly develop their resistance to these new macrolides, which has become a great threat to successful treatment of infectious diseases, such as infections of the respiratory system and urinary system. In this paper, total synthetic methods for MA that include erythromycin A (ERY), azithromycin (AZM), the clinical candidate solithromycin (CEM-101), as well as 14-membered and 15-membered azaketolides have been systematically reviewed on the basis of the literature reported previously. The total synthetic methods we describe here helps to accelerate the discovery of newer MA to deal with the serious problem of bacterial resistance.

The incidence of Metabolic Syndrome (MetS) has risen globally. MetS includes a combination of features, i.e. blood glucose impairment, excess abdominal/body fat dyslipidemia and elevated blood pressure. Other than conventional treatment with drugs, the main preventive approaches include lifestyle changes, weight loss, diet control and adequate exercise also proves to be beneficial. MicroRNAs (miRNAs) are small non-coding RNAs that play critical regulatory roles in most biological and pathological processes. In the present review, we discuss various miRNAs which are related to MetS by targeting various organs, including the pancreas, liver, skeletal muscles and adipose tissues. These miRNAs have the effect on insulin production and secretion (miR-9, miR-124a, miR-130a,b, miR152, miR-335, miR-375), insulin resistance (miR-29), adipogenesis (miR-143, miR148a) and lipid metabolism (miR-192). We also discuss the miRNAs as potential biomarkers and future therapeutic targets. This review may be beneficial for molecular biologists and clinicians dealing with MetS.