Quinolone Derivatives as Anticancer Agents: Importance in Medicinal Chemistry.

Quinolone is a heterocyclic compound containing carbonyl at the C-2 or C-4 positions with nitrogen at the C-1 position. The scaffold was first identified for its antibacterial properties, and the derivatives were known to possess many pharmacological activities, including anticancer. In this review, the quinolin-2(H)-one and quinolin-4(H)-one derivatives were identified to inhibit several various proteins and enzymes involved in cancer cell growth, such as topoisomerase, mi-crotubules, protein kinases, phosphoinositide 3-kinases (PI3K) and histone deacetylase (HDAC). Hybrids of quinolone with curcumin or chalcone, 2-phenylpyrroloquinolin-4-one and 4-quinolone derivatives have demonstrated strong potency against cancer cell lines. Additionally, quinolones have been explored as inhibitors of protein kinases, including EGFR and VEGFR. Therefore, this review aims to consolidate the medicinal chemistry of quinolone derivatives in the pipeline and discuss their similarities in terms of their pharmacokinetic profiles and potential target sites to provide an understanding of the structural requirements of anticancer quinolones.

Pharmacological advances in anti-retroviral therapy for human immunodeficiency virus-1 infection: A comprehensive review.

The discovery of anti-retroviral (ARV) drugs over the past 36 years has introduced various classes, including nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitor, fusion, and integrase strand transfer inhibitors inhibitors. The introduction of combined highly active anti-retroviral therapies in 1996 was later proven to combat further ARV drug resistance along with enhancing human immunodeficiency virus (HIV) suppression. As though the development of ARV therapies was continuously expanding, the variation of action caused by ARV drugs, along with its current updates, was not comprehensively discussed, particularly for HIV-1 infection. Thus, a range of HIV-1 ARV medications is covered in this review, including new developments in ARV therapy based on the drug's mechanism of action, the challenges related to HIV-1, and the need for combination therapy. Optimistically, this article will consolidate the overall updates of HIV-1 ARV treatments and conclude the significance of HIV-1-related pharmacotherapy research to combat the global threat of HIV infection.

A green and efficient synthetic methodology towards the synthesis of 1-allyl-6-chloro-4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives.

Quinolone is a privileged scaffold in medicinal chemistry and 4-Quinolone-3-Carboxamides have been reported to harbor vast therapeutic potential. However, conversion of N-1 substituted 4-Quinolone 3-Carboxylate to its corresponding carbamates is highly restrictive. This motivated us to adopt a much simpler, scalable and efficient methodology for the synthesis of highly pure N-1 substituted 4- Quinolone-3-Carboxamides with excellent yields. Our adopted methodology not only provides a robust pathway for the convenient synthesis of N-1 substituted 4- Quinolone-3-Carboxamides which can then be explored for their therapeutic potential, this may also be adaptable for the derivatization of other such less reactive carboxylate species.

Crohn's Disease: Potential Drugs for Modulation of Autophagy.

Autophagy is an intracellular process whereby cytoplasmic constituents are degraded within lysosomes. Autophagy functions to eliminate unwanted or damaged materials such as proteins and organelles as their accumulation would be harmful to the cellular system. Autophagy also acts as a defense mechanism against invading pathogens and plays an important role in innate and adaptive immunity. In physiological processes, autophagy is involved in the regulation of tissue development, differentiation and remodeling, which are essential for maintaining cellular homeostasis. Recent studies have demonstrated that autophagy is linked to various diseases and involved in pathophysiological roles, such as adaptation during starvation, anti-aging, antigen presentation, tumor suppression and cell death. The modulation of autophagy has shown greatest promise in Crohn's disease as most of autophagy drugs involved in these diseases are currently under clinical trials and some has been approved by Food and Drug Administration. This review article discusses autophagy and potential drugs that are currently available for its modulation in Crohn's disease.