Vladimir V. Kouznetsov

Recent Progress in the Synthesis of Quinolines

New developments in the chemistry of quinoline derivatives are reviewed. Two general synthetic routes based on the utilization of mono-substituted or ortho-substituted anilines are discussed. Their major methods and modifications are analyzed. syntheses. These classical syntheses are well-known and still frequently used for the preparation of pharmaceutical agents, ligands and functional materials bearing a quinoline backbone. However, current methods for quinoline synthesis often do not allow for adequate diversity and substitution on the quinoline ring system (19). Recent developments in the chemistry of quinoline derivatives have demonstrated that new metal-catalyzed coupling cyclizations or acid catalyzed cycloaddition of appropriate precursors could compete with classical syntheses in the efficacy and rapidity of the quinoline construction. These new developments have prompted us to review and analyze their major methods and modifications.

Recent developments in the design and synthesis of hybrid molecules based on aminoquinoline ring and their antiplasmodial evaluation.

A short history of hybrid molecules based on aminoquinolines gave interesting and important information useful for organic and medicinal chemistry, which are deeply involved in the design and development of new antimalarial agents. The highlights in the preparation of aminoquinoline antimalarials, their protocols and antiplasmodial activity and, specially, the development on hybridization approaches are represented.

In vitro antifungal activity of new series of homoallylamines and related compounds with inhibitory properties of the synthesis of fungal cell wall polymers

The synthesis, in vitro antifungal evaluation and SAR studies of 101 compounds of the 4-aryl-, 4-alkyl-, 4-pyridyl or -quinolinyl-4-N-arylamino-1-butenes series and related compounds, are reported here. Active structures showed to inhibit (1,3)-beta-D-glucan and mainly chitin synthases, enzymes that catalyze the synthesis of the major fungal cell wall polymers.

In vitro antifungal activity of polyfunctionalized 2-(hetero)arylquinolines prepared through imino Diels-Alder reactions.

Diverse polyfunctionalized quinolines, easily prepared using Lewis acid-catalyzed imino Diels-Alder reactions between corresponding aldimines, were tested for antifungal properties against standardized as well as clinical isolates of clinically important fungi. Among them, 4-pyridyl derivatives displayed the best activities mainly against dermatophytes. The activity appears not to be related neither to the lipophilicity nor to the basicity of compounds.

Synthesis and antimalarial activity of new heterocyclic hybrids based on chloroquine and thiazolidinone scaffolds

A series of new 21 chloroquine heterocyclic hybrids containing either benzylamino fragment or N-(aminoalkyl)thiazolidin-4-one moiety were synthesized and screened for their antimalarial activity against chloroquine (CQ)-sensitive 3D7 and multidrug-resistance Dd2 strains of Plasmodium falciparum. Although no compounds more active than CQ against 3D7 was found; against Dd2 strain, six compounds, four of them with benzylamino fragment, showed an excellent activity, up to 3-fold more active than CQ. Non specific cytotoxicity on J774 macrophages was observed in some compounds whereas only two of them showed liver toxicity on HepG2 cells. In addition, all active compounds inhibited the ferriprotoporphyrin IX biocrystalization process in concentrations around to CQ. In vivo preliminary results have shown that at least two compounds are as active as CQ against Plasmodium berghei ANKA.

Antimycobacterial susceptibility testing methods for natural products research.

The emergence of multidrug-resistant strains of Mycobacterium tuberculosis underscores the need of continuous developments on new and efficient methods to determine the susceptibility of isolates of M. tuberculosis in the search for novel antimicrobial agents. Natural products constitute an important source of new drugs, but design and implementation of antimycobacterial susceptibility testing methods are necessary for evaluate the different extracts and compounds. A number of biological assay methodologies are in current use, ranging from the classical disk diffusion and broth dilution assay format, to radiorespirometric (BACTEC), dye-based, and fluorescent/luminescence reporter assays. This review presents an analysis on the in vitro susceptibility testing methods developed for determinate antitubercular activity in natural products and related compounds (semi-synthetic natural products and natural products-derived compounds) and the criteria to select the adequate method for determination of biological activity of new natural products.

Synthesis and antifungal activity of diverse C-2 pyridinyl and pyridinylvinyl substituted quinolines

Diverse 2-pyridinyl quinolines 6-12 and 2-pyridinilvinyl quinolines 13-17 were prepared using a straightforward synthesis based on the BiCl(3)-catalyzed multicomponent imino Diels-Alder (imino DA) reaction or a novel tandem imino DA/catalytic tetrahydroquinoline ring oxidation/Perkin condensation sequential process. All members of the series showed activities against dermatophytes and some of them possessed a broad spectrum of action. 2-(Pyridin-4-yl)quinoline 9 and 2-(2-pyridin-4-yl)vinyl)quinoline 16 showed the best MIC(80) and MIC(50) against the clinically important fungi Candida albicans and non-albicans Candida species. In turn, 6-ethyl-2-(pyridin-2-yl)quinoline 6 showed the best properties against standardized as well as clinical strains of Cryptococcus neoformans.

Quinoline-based compounds as modulators of HIV transcription through NF-κB and Sp1 inhibition

18 quinoline-based compounds were tested for antiviral properties against human immunodeficiency syndrome (HIV). The compounds tested here contain quinoline or tetrahydroquinoline rings and can be divided into two main groups: group 1 includes 4-(2-oxopyrrolidinyl-1)-1,2,3,4-tetrahydroquinolines with 2-(3-nitrophenyl) substituent (N-series) or 2-(3-aminophenyl) moiety (H-series), and group 2 includes 2-(3-nitrophenyl)- or 2-(3-aminophenyl)-substituted quinolines (S-series). Two different antiviral assays were performed in order to test the anti-HIV activity of compounds: 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and recombinant virus assay (RVA). Results showed that the most active compounds were 2-aryl quinolines, particularly those containing methoxy substituents or no substituents in the quinoline skeleton. HIV transcription inhibition appears to be their target in both resting and phorbol myristate acetate (PMA) activated primary lymphocytes, and nuclear factor-kappaB (NF-kappaB) and specificity protein-1 (SP1) seems to be the most important transcription factors involved in their action.

An efficient synthesis of new C-2 aryl substituted quinolines based on three component imino Diels-Alder reaction

New effective approach to the synthesis of a wide variety of C-2 nitro or aminophenyl substituted quinolines was reported using diverse intermediate 4-(2-oxopyrrolinidyl-1)-tetrahydroquinolines that were prepared by a three component imino Diels-Alder reaction was reported. The key aromatisation process occurs cleanly with the loss of the 2-oxopyrrolinidyl-1 fragment.

A Straightforward Synthetic Approach to Antitumoral Pyridinyl Substituted 7H-Indeno[2,1-c]Quinoline Derivatives Via Three-Component Imino Diels- Alder Reaction

Abstract: A simple and efficient synthetic method of obtaining pyridinyl substituted indeno[2,1- c ]quinolinederivatives has been developed. This method involves a three-component imino Diels-Alder cycloadditionbetween anilines, pyridinecarboxyaldehydes and indene as the key ring forming step and subsequent treatmentof obtained 5,6,6a,11b-tetrahydroindeno[2,1- c ]quinolines with powdered sulfur to give correspondingindeno[2,1- c ]quinolines. Some of them were treated with potassium permanganate in acetone to afford the 7 H -indeno[2,1- c ]quinolin-7-ones. Most compounds of the series were devoid of antifungal properties against apanel of standard dermatophytes, however, nearly all of them were active against breast (MCF-7), lung (H-460)and central nervous system (SF-268) human cancer cell lines. Keywords: Multi-component reaction, imino Diels-Alder reaction, indeno[2,1- c ]quinolines, antitumoral and antifungalactivities. INTRODUCTION NNH ONH 3 CHOCH 3 Tetrahydroquinoline derivatives are an important class ofnatural and synthetic compounds, which have shown a widerange of biological activities [1] including antimalarial [2],antitumoral [3], antioxidant [4] and anti-inflammatory [5].Moreover, their polycyclic analogs such as indenoquinolinederivatives are used as potential pharmaceuticals [6]. Thus,many synthetic procedures have been developed to preparethese polycyclic quinoline systems [7], where theindeno[2,1-