Exploring quinoline-type inhibitors of ergosterol biosynthesis: Binding mechanism investigation via molecular docking, pharmacophore mapping, and dynamics simulation approaches.

Drug-resistant fungal infections pose a formidable challenge in healthcare, attributed to ergosterol production as a key mechanism of resistance. It is therefore imperative to target this pathway for effective therapeutic interventions. In this study, we have analyzed the binding mode of twelve quinoline derivatives known to be effective against various Candida species, Microsporum gypseum, and Cryptococcus neoformans.

Exploring acetaminophen prodrugs and hybrids: a review.

This critical review highlights the advances in developing new molecules for treating pain syndrome, an important issue for human health. Acetaminophen (APAP, known as paracetamol) and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in clinical practice despite their adverse effects. Research is being conducted to develop innovative drugs with improved pharmaceutical properties to mitigate these effects.

Pyrrolo[2,1-]isoquinoline scaffolds for developing anti-cancer agents.

Fused pyrrolo[2,1-]isoquinolines have emerged as compelling molecules with remarkably potent cytotoxic activity and topoisomerase inhibitors. This comprehensive review delves into the intricate world of this family of compounds, analyzing the natural marine lamellarins known for their diverse and complex chemical structures, exploring structure-activity relationships (SARs), and highlighting their remarkable versatility. The review emphasizes their fundamental role as topoisomerase inhibitors and cytotoxic agents, as well as some crucial aspects of the chemistry of pyrrolo[2,1-]isoquinolines, exploring synthetic strategies in total synthesis and molecular diversification trends, highlighting their importance in the field of medicinal chemistry and beyond.

Diastereoselective multicomponent synthesis of dihydroisoindolo[2,1-]quinolin-11-ones mediated by eutectic solvents.

In this contribution, a series of dihydroisoindolo[2,1-]quinolin-11-ones was synthesized by a one-pot multicomponent Povarov reaction starting from anilines, alkenes (-anethole, methyl eugenol and indene) and 2-formylbenzoic acid. Different eutectic solvents bearing Lewis or Brønsted acids were evaluated as reaction media and catalysts for the model reaction employing -toluidine and -anethole finding that the eutectic mixture ChCl/ZnCl (1/2) allowed the obtention of the target compound in 77% isolated yield. Under the optimized reaction conditions, 20 derivatives were obtained in good to moderated yields using - and -susbstituted anilines, while the corresponding -analogs followed a different pathway affording isoindolinones.

Influence of Substituents in a Six-Membered Chelate Ring of HG-Type Complexes Containing an N→Ru Bond on Their Stability and Catalytic Activity.

An efficient approach to the synthesis of olefin metathesis HG-type catalysts containing an N→Ru bond in a six-membered chelate ring was proposed. For the most part, these ruthenium chelates can be prepared easily and in high yields based on the interaction between 2-vinylbenzylamines and (the common precursor for Ru-complex synthesis). It was demonstrated that the increase of the steric volume of substituents attached to the nitrogen atom and in the α-position of the benzylidene fragment leads to a dramatic decrease in the stability of the target ruthenium complexes.

Synthesis, In Silico and In Vivo Toxicity Assessment of Functionalized Pyridophenanthridinones via Sequential MW-Assisted Intramolecular Friedel-Crafts Alkylation and Direct C-H Arylation.

A rapid, efficient, and original synthesis of novel pyrido[3,2,1-]phenanthridin-6-ones is reported. First, the key cinnamamide intermediates - were easily prepared from commercial substituted anilines, cinnamic acid, and 2-bromobenzylbromide in a tandem amidation and -alkylation protocol. Then, these -aryl--(2-bromobenzyl) cinnamamides - were subjected to a TFA-mediated intramolecular Friedel-Crafts alkylation followed by a Pd-catalyzed direct C-H arylation to obtain a series of potentially bioactive 4-phenyl-4,5-dihydro-6,8-pyrido[3,2,1-]phenanthridin-6-one derivatives - in good yields.

Microwave-assisted Synthesis of Pharmacologically Active 4-Phenoxyquinolines and their Benzazole-quinoline Hybrids Through SAr Reaction of 4,7-dichloroquinoline and Phenols Using [bmim][PF] as a Green Solvent.

Background: Quinoline and its derivatives have been shown to display a wide spectrum of biological properties, especially anticancer activity. Particularly, diverse potent anticancer drugs are based on the 4-phenoxyquinoline skeleton, acting as small-molecules VEGR2 and/or c-Met kinase inhibitors. However, the design of new drugs based on these quinoline derivatives remains a challenge.

Nanostructured silicate catalysts for environmentally benign Strecker-type reactions: and .

Chemical processes are usually catalytic transformations. The use of catalytic reagents can reduce the reaction temperature, decrease reagent-based waste, and enhance the selectivity of a reaction potentially avoiding unwanted side reactions leading to green technology. Chemical processes are also frequently based on multicomponent reactions (MCRs) that possess evident improvements over multistep processes.

Synthesis of endo-fused 5-unsubstituted Hexahydro-2H-pyrano[3,2-c]quinolinesvia Sequential Sc(OTf)-catalyzed Cationic Imino-Diels-Alder Reaction/N-debenzylation using N-benzylanilines, 3,4-dihydro-2H-pyran and Paraformaldehyde under MW Irradiation.

Background: Hexahydro-2H-pyrano[3,2-c]quinolines are known to have antibacterial, antifungal, and antitumor properties. Great efforts have been made to develop new synthetic methods that lead to the synthesis of valuable libraries. Extensive methodologies, low yields, excessive amounts of catalyst and expensive reactants are some of the limitations of current methodologies.

Application of New Efficient Hoveyda-Grubbs Catalysts Comprising an N→Ru Coordinate Bond in a Six-Membered Ring for the Synthesis of Natural Product-Like Cyclopenta[]furo[2,3-]pyrroles.

The ring rearrangement metathesis (RRM) of a - diastereomer mixture of methyl 3-allyl-3a,6-epoxyisoindole-7-carboxylates derived from cheap, accessible and renewable furan-based precursors in the presence of a new class of Hoveyda-Grubbs-type catalysts, comprising an N→Ru coordinate bond in a six-membered ring, results in the difficult-to-obtain natural product-like cyclopenta[]furo[2,3-]pyrroles. In this process, only one diastereomer with a -arrangement of the 3-allyl fragment relative to the 3a,6-epoxy bridge enters into the rearrangement, while the -isomers polymerize almost completely under the same conditions. The tested catalysts are active in the temperature range from 60 to 120 °C at a concentration of 0.

Synthesis of dihydroisoindolo[2,1-]quinolin-11-ones, their ADMET properties and antitumor activities.

We evaluated the antitumoral activity of diverse series of 5-aryl-dihydroisoindolo[2,1-]quinolin-11-ones, AIIQ (Aryl IsoIndolo-Quinoline, 4a-m), and 5-vinyl dihydroisoindolo[2,1-]quinolin-11-ones, VIIQ (Vinyl IsoIndolo-Quinoline, 6a-l), obtained using three component imino Diels-Alder (DA) reaction of anilines, -phthalaldehyde and dienophiles. The first series was obtained in previous work employing isoeugenol and anethole as dienophiles, whereas the vinyl series was synthesized in high yields (75-90%) using isoprene as a dienophile. The cytotoxic activity of both AIIQ and VIIQ series was evaluated against four cancer lines, identifying a new lead compound 4h from the AIIQ series, active against MCF-7 (310 nM), SKBR3 (1434 nM), PC3 (210 nM) and HeLa (79 nM) cells with high selectivity.

COVID-19 treatment: Much research and testing, but far, few magic bullets against SARS-CoV-2 coronavirus.

The new virus of the of β-Coronaviruses genus, SARS-CoV-2, is the causative agent of coronavirus disease-2019 (COVID-19) and is winning a proverbial chess match against all players simultaneous, including physicians, clinicians, pathologists, doctors, scientists, economists, athletes and politicians. The COVID-19 outbreak has seriously threatened public health, killing the most vulnerable persons and causing general panic. To stop this disease, effective remedies (i.

Pyridine and quinoline molecules as crucial protagonists in the never-stopping discovery of new agents against tuberculosis.

Tuberculosis (TB) disease remains to be an alarming infection worldwide with nearly 1.6 million deaths per year ranking above HIV/AIDS. Although Mycobacterium tuberculosis (Mtb), which causes TB, was identified more than 130 years ago, nowadays only old vaccine (Bacillus Calmette-Guérin vaccine) and classical toxic drugs that are losing its effectiveness are available in clinic practice.

Recent synthetic efforts in the preparation of 2-(3,4)-alkenyl (aryl) quinoline molecules towards anti-kinetoplastid agents.

Leishmaniasis, Chagas disease and African sleeping sickness have been considered some of the most important tropical protozoan afflictions. As the number of drugs currently available to treat these human illnesses is severely limited and the majority has poor safety profiles and complicated administration schedules, actually there is an urgent need to develop new effective, safe and cost-effective drugs. Because quinoline alkaloids with antiprotozoal activity (quinine, chimanine, cryptolepine or huperzine groups) were historically and are still essential models for drug research to combat these parasitic infections, synthetic or semi-synthetic quinoline-based molecules are important for anti-kinetoplastid drug design approaches and synthetic methods of their preparation become a key task that is the central subject of this review.

Bioactivity of semisynthetic eugenol derivatives against (Lepidoptera: Noctuidae) larvae infesting maize in Colombia.

The anti-acetylcholinesterase, larvicidal, antifeedant activities and general toxicity of 15 semisynthetic eugenol derivatives based on clove oil (including the own oil), were evaluated against the maize armyworm, (J.E. Smith).

Biomimetic Total Synthesis of Alkaloids.

A five-step total synthesis of alkaloids has been achieved using a biomimetic approach from zanthoxylamide protoalkaloids. The synthesis featured a direct amidation and a Bischler-Napieralski reaction to form the dihydroisoquinoline ring, which was then subjected to a Noyori asymmetric transfer hydrogenation to establish the stereogenic center at C-1. Our synthetic sequence provides an important perspective on the biosynthetic origin of alkaloids, since 6 natural alkaloids and 12 synthetic analogues were obtained with high enantioselectivity and in overall yields up to 68%.

Synthesis, Biological Evaluation and In Silico Computational Studies of 7-Chloro-4-(1-1,2,3-triazol-1-yl)quinoline Derivatives: Search for New Controlling Agents against (Lepidoptera: Noctuidae) Larvae.

The insecticidal and antifeedant activities of five 7-chloro-4-(1-1,2,3-triazol-1-yl)quinoline derivatives were evaluated against the maize armyworm, (J.E. Smith).

Anti-leishmanial effect of spiro dihydroquinoline-oxindoles on volume regulation decrease and sterol biosynthesis of Leishmania braziliensis.

Diverse spiro dihydroquinoline-oxindoles (JS series) were prepared using the BF•OEt-catalyzed imino Diels-Alder reaction between ketimine-isatin derivatives and trans-isoeugenol. Ten spiro-oxiindole derivatives were selected and evaluated at different stages of the life cycle of Leishmania braziliensis parasites, responsible for cutaneous leishmaniasis in South America. Among them, the 8'-ethyl-4'-(4-hydroxy-3-methoxyphenyl)-3'-methyl-3',4'-dihydro-1'H-spiro[indoline-3,2'-quinolin]-2-one called JS87 was able to inhibit the growth of promastigotes without affecting the mammalian cells viability, and to decrease the number of intracellular amastigotes of L.

Synthesis of zanthoxylamide protoalkaloids and their in silico ADME-Tox screening and in vivo toxicity assessment in zebrafish embryos.

Inspired by the simple and attractive structure of zanthoxylamide protoalkaloids: armatamide, rubecenamide, lemairamin, rubemamine and zanthosine; isolated from plants of the genus Zanthoxylum. We report the synthesis of a series of 29 substituted N-phenylethyl cinnamamides through the direct amidation of a variety of cinnamic acids with a broad range of phenylethylamines promoted by tris-(2,2,2-trifluoroethyl) borate (B(OCHCF)) in excellent yields and under mild reaction conditions. Then, the toxicological profile of the prepared compounds was studied through in silico computational methods, analyzing eight toxicity risks (hepatotoxicity, mutagenic, carcinogenicity, tumorigenic, immunotoxicity, cytotoxicity, irritant and reproductive effects) and two toxicity targets (AOFA and PGH1), while the acute toxicity toward zebrafish embryos (96 hpf-LC, 50% lethal concentration) was also determined in the present study.

Facile and highly diastereo and regioselective synthesis of novel octahydroacridine-isoxazole and octahydroacridine-1,2,3-triazole molecular hybrids from citronella essential oil.

A novel and highly efficient synthetic approach for the expedite construction of new octahydroacridine-isoxazole- and octahydroacridine-1,2,3-triazole-based molecular hybrids is first reported. Rapid access to the octahydroacridine core was achieved in a highly diastereoselective fashion via cationic Povarov reaction of N-propargyl anilines and citronella essential oil (Cymbopogon nardus). The subsequent 1,3-dipolar and Cu (I) catalyzed alkyne-azide cycloaddition reaction of the terminal alkyne fragment with the corresponding oxime or azide affords the desired 3,5-isoxazoles and 1,2,3-triazoles, respectively, as interesting molecular hybrid models for pharmacological studies.

In vitro 4-Aryloxy-7-chloroquinoline derivatives are effective in mono- and combined therapy against Leishmania donovani and induce mitocondrial membrane potential disruption.

The present study evaluates in vitro the effect of two synthetic compounds of the 7-chloro-4-aryloxyquinoline series, QI (CHClNO) and QII (CHClNOS), on Leishmania donovani parasites. The results obtained demonstrate that these compounds are able to inhibit the proliferation of L. donovani promastigotes in a dose-dependent way (QI IC = 13.

Alterations of mitochondrial electron transport chain and oxidative stress induced by alkaloid-like α-aminonitriles on Aedes aegypti larvae.

Aedes aegypti mosquitoes are responsible for dengue, chikungunya, and Zika virus transmission in tropical and subtropical areas around the world. Due to the absence of vaccines or antiviral drugs for human treatment, the majority of control strategies are targeted at Ae. aegypti elimination.

[Insecticidal action of synthetic girgensohnine analogues and essential oils on Rhodnius prolixus (Hemiptera: Reduviidae)].

Introduction: The alkaloid girgensohnine has been used as a natural model in the synthesis of new alkaloid-like alpha-aminonitriles with insecticidal effect against disease vectors.

Objective: To evaluate the biocide activity of girgensohnine analogues and essential oils of Cymbopogon flexuosus, Citrus sinensis and Eucalyptus citriodora in stage I and stage V Rhodnius prolixus nymphs.

Materials And Methods: We used a topical application model in tergites and sternites, as well as exposure to treated surfaces with different exploratory doses of each of the molecules and essential oils to determine the lethal doses (LD50 and LD95).

Behavior of detoxifying enzymes of Aedes aegypti exposed to girgensohnine alkaloid analog and Cymbopogon flexuosus essential oil.

Because mosquito control depend on the use of commercial insecticides and resistance has been described in some of them, there is a need to explore new molecules no resistant. In vivo effects of girgensohnine analog 2-(3,4-dimethoxyphenyl)-2-(piperidin-1-yl)acetonitrile DPPA and Cymbopogon flexuosus essential oil CFEO, on the detoxifying enzymes acetylcholinesterase (AChE), glutathione-S-transferase (GST), nonspecific esterases (α- and β-), mixed function oxidases (MFO) and p-NPA esterases were evaluated on a Rockefeller (Rock) and wild Aedes aegypti population from Santander, Colombia (WSant). The action was tested after 24h of exposure at concentrations of 20.