Current Development in the Synthesis of Benzimidazole-Quinoline Hybrid Analogues and their Biological Applications

Heterocyclic compounds have an essential role in many domains of medicinal chemistry. Many pharmaceutical industries use and investigate nitrogen-containing heterocycles because they are crucial in discovering and developing novel therapeutically active compounds. The benzimidazole moiety is a fundamental component of many heterocyclic scaffolds, which play an important role in producing a wide range of biological activities. Similarly, quinoline is also a versatile bicyclic heterocyclic scaffold with many medicinal applications. It is an essential scaffold for drug discovery leads, and it plays a significant role in medicinal chemistry and has biological activities similar to benzimidazole scaffolds. The present chapter discusses the quinoline-benzimidazole hybrids scaffolds and their potential pharmacological activities

Heterocycles

Heterocycles have constituted the largest area of research in organic chemistry. These heterocycles play an important role in biochemical processes because the side groups of the most typical and essential constituents of living cells, DNA and RNA, are based on aromatic heterocycles. Many synthetic methods have been developed for the preparation of heterocycles. The recent surge of interest in the chemistry of heterocycles can be explained by their unusual properties and exotic structure. These heterocycles include highly stable aromatic compounds that display physicochemical properties with relevance in the design of new materials. Thus, heterocycles contribute to the development of society from a biological and industrial point of view

ynthetic berberine derivatives as potential new drugs

The modern process of new drug discovery and development is an exciting, yet a challenging, endeavor. Although it can result in significant financial income and meet the medical needs of patients, it ultimately may result in failure. To achieve a fast and successful new product discovery and development process, natural products which are evolutionarily optimized as drug-like molecules have gained great attention as better potential sources of new chemical entities. Historically, plant species containing berberine are used in various traditional phytotherapy. However, despite the various therapeutic effects it exerts, berberine is not yet developed into a drug product. Addressing the barriers that hinder its successful development and the efforts made to overcome them is thus crucial. The toxicological and pharmacokinetic properties of berberine are the main barriers towards its development into a marketed drug product. It has low aqueous solubility, poor absorption, fast metabolism, and wide tissue distribution which lead to low bioavailability limiting its clinical application. Synthetic berberine derivatives with improved properties are suggested as better alternatives for further development and future therapeutic application. Hence, this paper summarizes the preclinical research studies conducted in the last decade to reveal the therapeutic potential of synthetic berberine derivatives for the treatment of various diseases and hence achieve successful berberine-based drug development in the future. To exploit the value of natural products as a source of leads for the development of effective drugs, collaboration among the different discovery and development scientists is essential

RECENT ADVANCES IN MOLECULAR MEDICINE AND TRANSLATIONAL RESEARCH

ABSTRACT BOO

NOVEL SMALL MOLECULE ANTIFUNGALS FOR INVASIVE FUNGAL INFECTIONS

Human fungal pathogens cause a range of diseases from benign skin conditions (i.e., ringworm) to thrush, mucosal membrane infections, and life-threatening systemic infections including bloodstream infections (i.e., aspergillosis and candidiasis) and Cryptococcal meningitis. These systemic infections occur most often in immunocompromised individuals and have high mortality rates. Current antifungal agents used in the clinic belong to three main classes: the polyenes (e.g., amphotericin B (AmB)), the echinocandins (e.g., caspofungin (CFG)), and the azoles (e.g., fluconazole (FLC)). In addition, the antimetabolite pyrimidine analogue flucytosine is used in combination with AmB. The three main classes class of antifungals each target different aspects of cell wall synthesis or cell membrane function and each class has different strengths and weaknesses depending on the strains of fungi that they are effective against, their route of administration, and their potential side effects. Problems associated with current antifungals include toxicity to patients, only effective against a limited spectrum of fungal strains, and the development of resistance of fungal strains to treatment. Discovering new antifungal therapies is a promising strategy to decrease mortality rates. Herein, three classes of molecules are evaluated for their potential as novel antifungals and reveal that (i) the antihistamines, terfenadine (TERF) and ebastine (EBA) improve the efficacy of azole antifungals when used in combination against a range of Candida strains, (ii) square-planar gold(I)-phosphine complexes exhibit broad-spectrum antifungal activity, and (iii) fluorinated aryl- and heteroaryl-substituted monohydrazones display broad-spectrum activity against fungi with little toxicity to mammalian cells, and (iv) other classes of molecules in recent literature that have shown antifungal activity. This work serves to identify promising scaffolds for novel classes of antifungals with the ultimate goal of bringing newer and more effective antifungals to be used clinically for systemic fungal infections

The synthesis, characterisation and antibacterial activity of benzimidazole-oxadiazole hybrids.

Masters Degree. University of KwaZulu-Natal, Durban.Abstract available in PDF

Recent advances in functionalized quinoline scaffolds and hybrids—Exceptional pharmacophore in therapeutic medicine

Quinoline is one of the most common nitrogen-containing heterocycles owing to its fascinating pharmacological properties and synthetic value in organic and pharmaceutical chemistry. Functionalization of this moiety at different positions has allowed for varying pharmacological activities of its derivative. Several publications over the last few decades have specified various methods of synthesis. This includes classical methods of synthesizing the primary quinoline derivatives and efficient methods that reduce reaction time with increased yield employing procedures that fulfill one of the twelve green chemistry principles, “safer solvent”. The metal nanoparticle-catalyzed reaction also serves as a potent and effective technique for the synthesis of quinoline with excellent atom efficiency. The primary focus of this review is to highlight the routes to synthesizing functionalized quinoline derivatives, including hybrids that have moieties with predetermined activities bound to the quinoline moiety which are of interest in synthesizing drug candidates with dual modes of action, overcoming toxicity, and resistance amongst others. This was achieved using updated literature, stating the biological activities and mechanisms through which these compounds administer relief. The ADMET studies and Structure-Activity Relationship (SAR) of novel derivatives were also highlighted to explore the drug-likeness of the quinoline-hybrids and the influence of substituent characteristics and position on the biological activity of the compounds