Antileishmanial activity of a new chloroquine analog in an animal model of Leishmania panamensis infection.

Leishmania panamensis is a relevant causative agent of tegumentary leishmaniasis in several Latin American countries. Available antileishmanial drugs have several limitations including relatively high toxicity, difficult administration, high production costs and the emergence of resistance in circulating strains. Therefore, the identification of new molecules as potential therapeutics for leishmaniasis is of great relevance.

Hexahydropyrrolo[2,3-]indole Compounds as Potential Therapeutics for Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia among the elderly and has become a leading public health concern worldwide. It represents a huge economic and psychological burden to caregivers and families. The presence of extracellular amyloid beta (Aβ) plaques is one of the hallmarks of this neurodegenerative disorder.

Antiviral Activity of Novel Quinoline Derivatives against Dengue Virus Serotype 2.

Dengue virus causes dengue fever, a debilitating disease with an increasing incidence in many tropical and subtropical territories. So far, there are no effective antivirals licensed to treat this virus. Here we describe the synthesis and antiviral activity evaluation of two compounds based on the quinoline scaffold, which has shown potential for the development of molecules with various biological activities.

Bioinspired chemical synthesis of monomeric and dimeric stephacidin A congeners.

Stephacidin A and its congeners are a collection of secondary metabolites that possess intriguing structural motifs. They stem from unusual biosynthetic sequences that lead to the incorporation of a prenyl or reverse-prenyl group into a bicyclo[2.2.

Assessment of Novel Curcumin Derivatives as Potent Inhibitors of Inflammation and Amyloid-β Aggregation in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting the elderly population worldwide. Brain inflammation plays a key role in the progression of AD. Deposition of senile plaques in the brain stimulates an inflammatory response with the overexpression of pro-inflammatory mediators, such as the neuroinflammatory cytokine.

Organocatalytic Synthesis of Methylene-Bridged N-Heterobiaryls.

A one-step synthesis of 1,1'- and 2,2'-methylene-bridged N-heterobiaryls directly from the corresponding N-heterocycles in a reaction with methylmagnesium chloride in the presence of catalytic amounts of N,N,N',N'-tetramethylethylenediamine under thermal and microwave conditions is reported. The split-and-merge methylenation of 2,2'-N-heterobiaryls and the direct ortho-alkylation of quinoline and isoquinoline with Grignard reagents have also been developed. Mechanistic studies identified several intermediates and provided insight into the formation and roles of magnesium hydride species in the process.

Mechanistic insights into the potassium tert-butoxide-mediated synthesis of N-heterobiaryls.

We report herein that symmetrical and non-symmetrical N-heterobiaryls are produced by a potassium tert-butoxide-mediated dimerization of heterocyclic N-oxides. The reaction is scalable and transition metal-free, and can be carried out under thermal and microwave conditions. Preliminary mechanistic studies point to the involvement of radical anionic intermediates arising from the N-oxide substrates and potassium tert-butoxide.

Insights into the structural patterns of the antileishmanial activity of bi- and tricyclic N-heterocycles.

The influence of various structural patterns in a series of novel bi- and tricyclic N-heterocycles on the activity against Leishmania major and Leishmania panamensis has been studied and compounds that are active in the low micromolar region have been identified. Both quinolines and tetrahydrooxazinoindoles (TOI) proved to have significant antileishmanial activities, while substituted indoles were inactive. We have also showed that a chloroquine analogue induces Leishmania killing by modulating macrophage activation.

Recent Advances in the C-H-Functionalization of the Distal Positions in Pyridines and Quinolines.

This review summarizes recent developments in the C-H-functionalization of the distal positions of pyridines, quinolines and related azaheterocycles. While the functionalization of the C2 position has been known for a long time and is facilitated by the proximity to N1, regioselective reactions in the distal positions are more difficult to achieve and have only emerged in the last decade. Recent advances in the transition metal-catalyzed distal C-H-functionalization of these synthetically-important azaheterocycles are discussed in detail, with the focus on the scope, site-selectivity and mechanistic aspects of the reactions.

Concise Total Synthesis of Trichodermamides A, B, and C Enabled by an Efficient Construction of the 1,2-Oxazadecaline Core.

We report herein a facile and efficient method of the construction of the cis-1,2-oxazadecaline system, distinctive of (pre)trichodermamides, aspergillazine A, gliovirin, and FA-2097. The formation of the 1,2-oxazadecaline core was accomplished by a 1,2-addition of an αC-lithiated O-silyl ethyl pyruvate oxime to benzoquinone, which is followed by an oxa-Michael ring-closure. The method was successfully applied to the concise total synthesis of trichodermamide A (in gram quantities) and trichodermamide B, as well as the first synthesis of trichodermamide C.

Experimental and mechanistic analysis of the palladium-catalyzed oxidative C8-selective C-H homocoupling of quinoline N-oxides.

A novel site-selective palladium-catalyzed oxidative C8-H homocoupling reaction of quinoline N-oxides has been developed. The reaction affords substituted 8,8'-biquinolyl N,N'-dioxides that can be readily converted to a variety of functionalized 8,8'-biquinolyls. Mechanistic studies point to the crucial role of the oxidant and a non-innocent behavior of acetic acid as a solvent.

Palladium-Catalyzed C8-Selective C-H Arylation of Quinoline -Oxides: Insights into the Electronic, Steric and Solvation Effects on the Site-Selectivity by Mechanistic and DFT Computational Studies.

We report herein a palladium-catalyzed C-H arylation of quinoline -oxides that proceeds with high selectivity in favor of the C8-isomer. This site-selectivity is unusual for palladium, since all of the hitherto described methods of palladium-catalyzed C-H functionalization of quinoline -oxides are highly C2-selective. The reaction exhibits a broad synthetic scope with respect to quinoline -oxides and iodoarenes and can be significantly accelerated to sub-hour reaction times under microwave irradiation.

Straightforward Access to Hexahydropyrrolo[2,3-]indole Core by a Regioselective C3-Azo Coupling Reaction of Arenediazonium Compounds with Tryptamines.

A base-mediated regioselective electrophilic addition of arenediazonium salts at the C3-position of tryptamines followed by cyclization provides an efficient entry to C3-nitrogenated hexahydropyrrolo[2,3-]indoles (HPIs) that can subsequently be transformed into 3-arylhexahydropyrrolo[2,3-]indoles and other HPI derivatives. The reaction is the first example of a 1,2-diamination that utilizes easily accessible arenediazonium salts as nitrogenous electrophiles.

Synthetic and mechanistic aspects of the regioselective base-mediated reaction of perfluoroalkyl- and perfluoroarylsilanes with heterocyclic N-oxides.

The scope and mechanistic implications of the direct transformation of heterocyclic N-oxides to 2-trifluoromethyl-, and related perfluoroalkyl- and perfluoroaryl-substituted N-heterocycles has been studied. The reaction is effected by perfluoroalkyl- and perfluorophenyltrimethylsilane in the presence of strong base. In situ displacement of the para-fluoro substituent in the pentafluorophenyl ring and the methoxy group in 8-methoxyquinolines with additional nucleophiles allows for further site-selective refunctionalization of the N-heterocyclic products.