Current Topics in Medicinal Chemistry - Volume 21, Issue 17, 2021

Tea, a worldwide popular beverage rich in polyphenols, contributes to the prevention of many diseases and thus is beneficial to human health. Tea is a product through processing the fresh leaves picked from the plant Camellia sinensis (C. sinensis, genus Camellia section Thea). To date, systematic studies have been conducted on the phytochemicals from more than 20 tea varieties and related tea products, resulting in the structural determination of over 400 constituents viz. different types of polyphenols, purines, and their derivatives, mono to tetra-terpenoids, and minor other phytomolecules. These various tea phytochemicals contribute to the anti-oxidative effects, anti-diabetes, anti-inflammation, anti-cancer, blood lipid reduction, neuroprotection, anti-Alzheimer's disease, hepatoprotection, and anti-microbial activities, etc. Staphylococcus aureus (S. aureus), the significant human pathogens, could cause nosocomial and community-acquired infections, which is also responsible for various infectious diseases from mild to severe life-threatening conditions, such as bacteremia (bloodstream infection), endocarditis (heart valves infection), pneumonia, and meningitis (brain infection), leading to 2% clinical disease in of all patient admissions. The multidrug resistance (MDR) and antibiotics losing efficacy, esp. in methicillin resistance Staphylococcus aureus (MRSA) urge for novel antimicrobial agents. The MRSA strains are resistant to the entire class of β-lactam antibiotics and limit effective treatment, leading to still spread of staphylococcal infections. MRSA also exhibits resistance to cephalosporins, macrolides, fluoroquinolones, aminoglycosides, and glycopeptides (teicoplanine and vancomycin), leading to resistant strains-glycopeptide resistant strain (GRSA) and glycopeptide intermediate (GISA) S. aureus. In this review, chemical constituents responsible for the anti-MRSA activity of tea are explored.

Since a variety of benzo-fused nitrogen- and oxygen-based bioactive heterocyclic moieties are present in the form of benzoxazinones, spirooxindole-based heterocyclic compounds, coumarinfused heterocyclic compounds, and 2H-indazoles, this review article briefly describes some of the major advancements and developments in the area of 1,4-benzoxazine-3-ones, 1,4-benzoxazin-2- ones, spiropyrrolidine and spiropyrrolizine-based ring compounds, coumarin-fused compounds, benzopyran- fused coumarins and a 2H-indazoles class of bioheterocycles. Thus, keeping in view the medicinal importance of these bioactive benzo-fused heterocycles, special attention has been given to their synthesis as well as medicinal/pharmaceutical properties in detail.

Plant-endophyte associations represent an inexhaustible source of novel metabolites, exhibiting significance in environment, agriculture and pharmaceutical perspectives. The global outbreak of life-threatening diseases necessitates a need for a more targeted approach through efficient drug-discovery programs. In recent times, endophytes as “bio-factories” have been extensively explored for the production of novel bioactive metabolites demonstrating therapeutic properties. Resources in computational biology co-integrated with combinational chemistry have made significant contributions in this field, aiding in discovery and screening of potential “drug-like” molecules from endophytes. The review provides a meta-analysis of bioactive metabolite production from endophytes, extensively discussing the bio-prospection of natural products for pharmaceutical applications. In light of emerging importance of endophytes as anti-infective agents, an exploration of the pharmaceutical design of novel chemical entities and analogues has enabled efficient and cost-effective drug discovery programs. However, bottlenecks in endophyte biology and research require a better understanding of endophyte dynamics and mechanism of bioactive metabolite production towards a sustainable drug discovery program.

Tetrahydroquinoline and isoquinoline scaffolds are important class of heterocyclic compounds, which is implied for the development of new drugs and diagnostic for therapeutic function. Naturally occurring as well as synthetic tetrahydroquinolines/isoquinolines possess many different biological activities and have been testified as remarkable cytotoxic and potency in human cancer cell lines. Tetrahydroquinoline/isoquinoline based compounds displayed a key role in the development of anticancer drugs or lead molecules and acting through various mechanisms such as cell proliferation, apoptosis, DNA fragmentation, inhibition of tubulin polymerization, induced cell cycle arrest, interruption of cell migration, and modulation. The number of tetrahydroquinoline/isoquinoline derivatives has been reported as potent anticancer agents. Due to promising anticancer activities and wideranging properties of these molecules, we have compiled the literature for the synthesis and anticancer properties of various tetrahydroquinolines and isoquinolines. We have reported the synthesis of potent tetrahydroquinoline/isoquinoline molecules of the last 10 years with their anticancer properties in various cancer cell lines and stated their half-maximal inhibitory concentration (IC50). In addition, we also considered the discussion of molecular docking and structural activity relationship wherever provided to understand the possible mode of activity a target involved and structural feature responsible for the better activity, so the reader can directly find the detail for designing new anticancer agents.