Inhibition of cancer cells by Quinoline-Based compounds: A review with mechanistic insights.

This article includes a thorough examination of the inhibitory potential of quinoline-based drugs on cancer cells, as well as an explanation of their modes of action. Quinoline derivatives, due to their various chemical structures and biological activity, have emerged as interesting candidates in the search for new anticancer drugs. The review paper delves into the numerous effects of quinoline-based chemicals in cancer progression, including apoptosis induction, cell cycle modification, and interference with tumor-growth signaling pathways. Mechanistic insights on quinoline derivative interactions with biological targets enlightens their therapeutic potential. However, obstacles such as poor bioavailability, possible off-target effects, and resistance mechanisms make it difficult to get these molecules from benchside to bedside. Addressing these difficulties might be critical for realizing the full therapeutic potential of quinoline-based drugs in cancer treatment.

Synthesis of fused polycyclic ß-carboline derivatives using Ugi-4CR followed by cascade cyclization.

Ugi-four component reaction (Ugi-4CR) is extremely attractive for diversity-oriented and step economical synthesis as evident from past applications. Here we report the synthesis of fused polycyclic ß-carboline derivatives by sequential Pictet-Spengler's and Ugi-4CR multi-component reaction followed by cascade cyclization. The post cyclisation of Ugi product provides conformationally stable heterocyclic molecule that is expected to be suitable for interaction with different biological targets. The methodology provides a simple and facile access to heterocycles embedded in polycyclic framework which otherwise seems difficult to synthesize by conventional methods. Synthesis of fused Polycyclic ß-Carboline Derivatives Using Ugi-4CR Followed by Cascade Cyclization.

Asymmetric Reactions of N-Phosphonyl/Phosphoryl Imines.

The asymmetric reactions of imines continued to attract the attention of the scientific community for decades. However, the stereoselective reactions of N-phosphonyl/phosphoryl imines remained less explored as compared to other N-substituted imines. The chiral auxiliary-based asymmetric-induction strategy with N-phosphonyl imines could effectively generate enantio- and diastereomeric amine, α,ß-diamine, and other products through various reactions. On the other hand, the asymmetric approach for the generation of chirality through the utilization of optically active ligands, along with metal catalysts, could be successfully implemented on N-phosphonyl/phosphoryl imines to access numerous synthetically challenging chiral amine scaffolds. The current review critically summarizes and reveals the literature precedence of more than a decade to highlight the major achievements existing to date that can display a clear picture of advancement as well drawbacks in this area.

An atom-economical and regioselective metal-free C-5 chalcogenation of 8-aminoquinolines under mild conditions.

A general and simple metal-free protocol for expedient C-H functionalization leading to the regioselective generation of C-5 chalcogenated 8-aminoquinoline analogues in up to 90% yield at room temperature (25 °C) has been established. This methodology is an eco-friendly approach to the atom-economical utilization of diaryl/dialkyl chalcogenides for direct access to chalcogenated quinolines and is scalable to the gram scale without considerable decrease in the yield of the product. It represents a practical alternative to the existing metal-catalyzed functionalization of 8-aminoquinoline derivatives with broad functional group tolerance. The controlled experiments suggest that the reaction possibly proceeds through an ionic pathway at room temperature. Furthermore, the potentiality for the functionalization of free amines in chalcogenated-8-aminoquinolines provides an attractive perspective for further elaboration of the amine substituent through chemical manipulations. The applicability of the standardized method has been augmented through late-stage antimalarial drug diversification of primaquine analogues.

Pd-Catalyzed regioselective intramolecular dehydrogenative C-5 cross coupling in an N-substituted pyrrole-azole system.

Functionalized polycyclic pyrrole-azole structures possessing fused six membered and seven membered rings were directly synthesized via ligand-enabled, Pd-catalyzed, site selective, intramolecular cross couplings of N-substituted pyrrole-azoles. C5-H activation in the presence of a reactive C2-H remains a challenge that needs to be addressed and this was targeted to be resolved through the present approach by specifically generating the cyclized products with 83-100% selectivity. The featured methodology provides a novel disconnection for the synthesis of pyrrole containing alkaloids and medicinal compounds.

Microwave-Induced Synthesis of Bioactive Nitrogen Heterocycles.

There are many different applications of heterocyclic molecules in the pharmaceutical and materials science fields, which make them an important family of compounds. Among these heterocyclic compounds, nitrogen-containing heterocyclic (N-heterocyclic) compounds have attracted a lot of interest among researchers due to their various applications across a wide variety of fields. Many studies have been performed over the past few years to study the synthesis of N-heterocycles under different reaction conditions, such as solvent-free, catalytic, reactants immobilized on a solid support, one-pot synthesis, and microwave irradiation. It has been demonstrated by our research group that microwaves can be utilized for rapid and efficient synthesis of biologically active compounds. In this review, we provide an overview of the microwave-assisted non-catalytic and catalytic preparation of nitrogen-containing heterocycles, mostly polycyclic N-heterocycles, five-membered N-heterocycles, six-membered N-heterocycles, and fused N-heterocycles. Mostly in this article, we explore the microwave-assisted preparation of biologically important compounds, such as pyrimidines, thiazoles, imines, tetrazoles, steroidal derivatives, quinolines, indolizine, triazoles, beta-lactams, pyrroles and quinoxalines.

Solar Light-Induced Synthesis of Biologically Active Compounds.

Over the past few years, photocatalytic methods have shown great promise as low-cost, environmentally friendly, and sustainable technologies. During the development of photochemistry, a variety of sources of light were used, including sunlight, compact fluorescent lamps, lasers, and even light-emitting diodes. As a part of preparing diverse organic compounds, the photochemical approach was used, for instance, to form rings, arylated compounds, cycloaddition, functionalized compounds, dehalogenated compounds, oxidized compounds, reduced compounds, isomers, and sensitized compounds. Solar energy is a renewable resource that can be harvested from the sun and this light energy can be changed into chemical energy with the help of photocatalysts. During this green approach, electron-hole pairs are generated in photocatalysts in order to begin reactions by using solar light. It has been highlighted in this article that there have been impressive developments in the use of light, mainly the solar light, to promote important organic reactions, which would otherwise be unattainable under thermal conditions.

Unveiling the Significance of tert-Butoxides in Transition Metal-Free Cross-Coupling Reactions.

The astounding reactivity of tert-butoxides in transition metal-free coupling reactions is driving the scientific community towards a new era of environmental friendly, as well as cost-effective, transformation strategies. Transition metal-catalyzed coupling reactions generate hazardous wastes and require harsh reaction conditions, mostly at elevated temperature, which increases not only costs but also environmental concerns regarding the methodology. Tert-butoxide-catalyzed/mediated coupling reactions have several advantages and potential applications. They can form carbon-carbon, carbon-heteroatom, and heteroatom-heteroatom bonds under mild reaction conditions. Mechanistic insights into these reactions include both ionic and radical pathways, with the fate of the intermediates depending on the reaction conditions and/or additives used in the reactions. Among all of the known tert-butoxides, potassium tert-butoxide has pronounced applications in transition metal-free coupling reactions as compared to other tert-butoxides, such as sodium and lithium tert-butoxides, because of the higher electropositivity of potassium compared to sodium and lithium. Moreover, potassium tert-butoxide can act as a source of base, nucleophile and single electron donors in various important transformations. In this review, we provide an extensive overview and complete compilation of transition metal-free cross-coupling reactions catalyzed/promoted by tert-butoxides during the past 10 years.

Recent Advances in the Green Synthesis of Active N-Heterocycles and Their Biological Activities.

N-heterocyclic scaffolds represent a privileged architecture in the process of drug design and development. It has widespread occurrence in synthetic and natural products, either those that are established or progressing as potent drug candidates. Additionally, numerous novel N-heterocyclic analogues with remarkable physiological significance and extended pharmaceutical applications are escalating progressively. Hence, the classical synthetic protocols need to be improvised according to modern requirements for efficient and eco-friendly approaches. Numerous methodologies and technologies emerged to address the green and sustainable production of various pharmaceutically and medicinally important N-heterocyclic compounds in last few years. In this context, the current review unveils greener alternatives for direct access to categorically differentiated N-heterocyclic derivatives and its application in the establishment of biologically active potent molecules for drug design. The green and sustainable methods accentuated in this review includes microwave-assisted reactions, solvent-free approaches, heterogeneous catalysis, ultrasound reactions, and biocatalysis.

Design and identification of novel annomontine analogues against SARS-CoV-2: An in-silico approach.

AIMS: COVID-19 has currently emerged as the major global pandemic affecting the lives of people across the globe. It broke out from Wuhan Province of China, first reported to WHO on 31st December 2019 as "Pneumonia of unknown cause". Over time more people were infected with this virus, and the only tactic to ensure safety was to take precautionary measures due to the lack of any effective treatment or vaccines. As a result of unavailability of desired efficacy for previously repurposed drugs, exploring novel scaffolds against the virus has become the need of the hour. MAIN METHODS: In the present study, 23 new annomontine analogues were designed representing ß-Carboline based scaffolds. A hypothesis on its role as an effective ligand was laid for target-specific binding in SARS-CoV-2. These molecules were used for molecular docking analysis against the multiple possible drug targets using the Maestro Interface. To ensure the drug safety of these molecules ADME/Tox analysis was also performed. KEY FINDINGS: The molecular docking analysis of the 23 novel molecules indicated the efficiency of these derivates against COVID-19. The efficiency of molecules was computed by the summation of the docking score against each target defined as LigE Score and compared against Hydroxycholoquine as a standard. Based on the docking score, the majority of the annomontine derivatives were found to have increased binding affinity with targets as compared to hydroxycholoquine. SIGNIFICANCE: Due to the lack of efficiency, effectiveness, and failure of already repurposed drugs against the COVID-19, the exploration of the novel scaffold that can act as effective treatment is much needed. The current study hence emphasizes the potential of Annomontine based - ß- Carboline derivatives as a potential drug candidate against COVID-19.

Synthesis of unnatural amino acid derivatives via palladium catalyzed 1,4 addition of boronic acids.

Aryl and alkenyl amino acid derivatives were synthesized by a palladium catalyzed 1,4 addition of the corresponding boronic acids to 2-acetamidoacrylate.

Novel synthetic approach toward (+/-)-beta-cuparenone via palladium-catalyzed tandem Heck cyclization of 1-bromo-5-methyl-1-aryl-hexa-1,5-dien-3-ol derivatives.

A novel and convenient synthetic route toward (+/-)-beta-cuparenone and many other sesquiterpene natural product precursors has been developed via palladium-catalyzed tandem Heck cyclization of 1-bromo-5-methyl-1-aryl-hexa-1,5-dien-3-ols. [reaction: see text].

Ligand-promoted intramolecular dehydrogenative cross-coupling using a Cu catalyst: direct access to polycyclic heteroarenes.

A copper(II)-promoted intramolecular C-H coupling reaction between indole-2 and imidazole-2 moieties has been developed for polycyclic heteroarene synthesis. The method provides direct access to biheteroaryl incorporated polycyclic frameworks, which are of huge interest in the area of functional materials and drug-discovery.

1,3-Dipolar cycloaddition of 4-platinumisochromenyliums with an olefin and tandem insertion into benzylic C-H bonds.

Isochromenylium-4-ylplatinum(II) species, generated from 1-(2-alkynylphenyl)hex-5-en-1-ones and Pt(II), reacted with a pendant olefin via [3+2] cycloaddition to form tetracyclic Pt-carbene complexes, which underwent C-H insertion with a benzyloxy group at δ or ε positions to give highly complex polycycles, which are otherwise hard to access.

Phosphorous pentoxide mediated synthesis of 5-HMF in ionic liquid at low temperature.

A convenient, mild and environment-friendly dehydration reaction of fructose in ionic liquid using phosphorous pentoxide (P(2)O(5)) has been investigated. The acidic nature of P(2)O(5) along with its hygroscopic properties has been successfully utilized to afford 81.2% yield of 5-hydroxymethylfurfural (5-HMF) at 50°C in 60 mins. Phosphoric acid yielded remarkably less 5-HMF even at higher temperature and longer reaction times. The reaction was optimized by varying different parameters and the results indicated that no rehydration products, such as levulinic acid or formic acid, were formed.