Mini Reviews in Medicinal Chemistry - Volume 19, Issue 6, 2019

Hybrid molecule approach of drug design has become popular due to advantages such as delayed resistance, reduced toxicity, ease of treatment of co-infection and lower cost of preclinical evaluation. Antifungal drugs currently available for the treatment of fungal diseases suffer a major side effect of drug resistance. Hybrid drugs development is one of the approaches that has been employed to control microbial resistance. Their antifungal activity is influenced by their design. This review is focused on hybrid molecules exhibiting antifungal properties to guide scientists in search of more efficient drugs for the treatment of fungal diseases.

Natural medicines are widely utilized in human healthcare. Their beneficial effects have been attributed to the existence of natural active ingredients (NAI) with a positive impact on disease treatment and prevention. Public awareness about the side effects of synthetic chemical compounds increased the need for NAI as well. Clinical applications of NAI are limited by their instability and poor water solubility, while micronization is a major strategy to overcome these drawbacks. Supercritical carbon dioxide (sc-CO2) based nano techniques have drawn great attention in nanomedicinal area for many years, due to their unique characters such as fast mass transfer, near zero surface tension, effective solvents elimination, non-toxic, non-flammable, low cost and environmentally benign. In terms of functions of sc-CO2, many modified sc-CO2 based techniques are developed to produce NAI nanoparticles with high solubility, biological availability and stability. 5 types of promising methods, including gas-assisted melting atomization, CO2-assisted nebulization with a bubble dryer, supercritical fluidassisted atomization with a hydrodynamic cavitation mixer, supercritical CO2-based coating method and solution-enhanced dispersion by sc-CO2 process, are summarized in this article followed by a highlight of their fundamental synthesis principles and important medicinal applications.

1,3,4-Oxadiazole, a five-membered aromatic ring can be seen in a number of synthetic molecules. The peculiar structural feature of 1,3,4-oxadiazole ring with pyridine type of nitrogen atom is beneficial for 1,3,4-oxadiazole derivatives to have effective binding with different enzymes and receptors in biological systems through numerous weak interactions, thereby eliciting an array of bioactivities. Research in the area of development of 1,3,4-oxadiazole-based derivatives has become an interesting topic for the scientists. A number of 1,3,4-oxadiazole based compounds with high therapeutic potency are being extensively used for the treatment of different ailments, contributing to enormous development value. This work provides a systematic and comprehensive review highlighting current developments of 1,3,4-oxadiazole based compounds in the entire range of medicinal chemistry such as anticancer, antifungal, antibacterial, antitubercular, anti-inflammatory, antineuropathic, antihypertensive, antihistaminic, antiparasitic, antiobesity, antiviral, and other medicinal agents. It is believed that this review will be of great help for new thoughts in the pursuit for rational designs for the development of more active and less toxic 1,3,4-oxadiazole based medicinal agents.

After restricting the proliferation of CD4+T cells, Human Immunodeficiency Virus (HIV), infection persists at a very fast rate causing Acquired Immunodeficiency Syndrome (AIDS). This demands the vigorous need of suitable anti-HIV agents, as existing medicines do not provide a complete cure and exhibit drawbacks like toxicities, drug resistance, side-effects, etc. Even the introduction of Highly Active Antiretroviral Therapy (HAART) failed to combat HIV/AIDS completely. The major breakthrough in anti-HIV discovery was marked with the discovery of raltegravir in 2007, the first integrase (IN) inhibitor. Thereafter, the discovery of elvitegravir, a quinolone derivative emerged as the potent HIV-IN inhibitor. Though many more classes of different drugs that act as anti-HIV have been identified, some of which are under clinical trials, but the recent serious focus is still laid on quinoline and its analogues. In this review, we have covered all the quinoline-based derivatives that inhibit various targets and are potential anti-HIV agents in various phases of the drug discovery.

Background: Thiazoles and pyridines are versatile synthetic scaffolds possessing wide spectrum of biological effects including potential antimicrobial activity. Objective: In the efforts to develop suitable antimicrobia drugs, medicinal chemists have focused on thiazole derivatives. A novel series of 2-thiazolyl pyridines was prepared in a one-pot three-component reaction using 2-bromoacetyl pyridine as a starting precursor. Method: Structure of the synthesized compounds was elucidated by spectral data (FT-IR, 1H NMR, 13C NMR, and mass) and elemental analyses. The prepared compounds were screened for their in vitro antimicrobial activity. Results: The results revealed that compounds 4a,b,e-g and 12 showed promising activity. Molecular docking studies using MOE software were carried out for compounds 4a and 4b which exhibited potent activities indicated by the diameter zones (4a; 3.6, 4.0, 1.2 mm) (4b; 4.2, 3.5, 1.5 mm) and the binding affinities (4a; -5.7731, -5.3576, -4.6844 kcal mol-1) (4b; -5.9356, -2.8250, -5.3628 kcal mol-1) against Candida albicans, Bacillus subtilis and Escherichia coli, respectively. Conclusion: This paper describes a facile and efficient MCR for synthesis of 2-thiazolyl pyridines from reaction of 2-bromoacetyl pyridine with different reagents. There was an agreement between the values of binding affinities and interactions and the data obtained from the practical antimicrobial screening of the tested compounds.