Diorganyl diselenides: a powerful tool for the construction of selenium containing scaffolds.

Organoselenium compounds find versatile applications in organic synthesis, materials synthesis, and ligand chemistry. Organoselenium heterocycles are widely studied agents with diverse applications in various biological processes. This review highlights the recent progress in the synthesis of selenium heterocycles using diorganyl diselenides with keen attention on green synthetic approaches, scopes, C-H selanylation, the mechanisms of different reactions and insights into the formation of metal complexes. The C-H selanylation using diorganyl diselenides with different catalysts, bases, transition metals, iodine salts, NIS, hypervalent iodine, and other reagents is summarised. Finally, the diverse binding modes of bis(2/4-pyridyl)diselenide with different metal complexes are also summarised.

Synthesis of selenated tetracyclic indoloazulenes via iodine and diorganyl diselenides.

Herein, we report an efficient protocol for the synthesis of selenated tetracyclic indoloazulenes. The reaction of diorganyl diselenides with molecular iodine in dichloromethane leads to the in situ formation of organo selenenyl iodide. The synthesis of selenylated tetracyclic indoloazulenes through intramolecular cascade cyclization has been achieved via organo selenenyl iodide and bisindole at room temperature under metal-free conditions in good yields. All compounds were fully characterized by the FT-IR, HRMS, and 1H, 13C and 77Se NMR spectral data.

Synthesis of [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-oxadiazole derivatives as potent antiproliferative agents via a hybrid pharmacophore approach.

Imiquimod (1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine) is efficacious in topical therapy for certain types of skin cancers. Structurally similar EAPB0203 (N-methyl-1-(2-phenethyl)imidazo[1,2-a]quinoxalin-4-amine) has been shown higher in vitro potency than imiquimod. Besides, triazole, oxadiazole, and thiadiazole rings are privileged building blocks in drug design. A series of [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-oxadiazole and [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-thiadiazole derivatives were therefore synthesized by incorporation of these rings into the structure of EAPB0203 and assessed their antiproliferative effects against various cancer cell lines. The 1,3,4-oxadiazole derivatives demonstrated the superior effectiveness compared to imiquimod and EAPB0203. Our findings highlight the excellent potential of [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-oxadiazole derivatives as anticancer agents.

Design and synthesis of quinoxaline-1,3,4-oxadiazole hybrid derivatives as potent inhibitors of the anti-apoptotic Bcl-2 protein.

Quinoxaline is one of the privileged heterocyclic fragments for drug molecules. Quinoxaline anticancer drug candidates XK469 and CQS exhibit antiproliferative and proapoptotic properties against various cancers. Based on their chemical structures, we therefore synthesized a series of quinoxaline-1,3,4-oxadiazole hybrids and assessed their anticancer potential on human leukemia HL-60 cells. Although these hybrids exerted significant inhibition of HL-60 cell proliferation, they showed high cytotoxicity on human normal cells (WI-38). Utilizing information from molecular modelling of the hybrids to the anti-apoptotic Bcl-2 protein, we added substructures including phenyl, piperazine, piperidine, and morpholine rings to their frameworks. The designed quinoxaline-1,3,4-oxadiazole hybrid derivatives successfully induced apoptotic response on HL-60 cells with low toxicity on WI-38 cells. Furthermore, RT-PCR analysis demonstrated that these derivatives predominantly inhibit Bcl-2 expression. Our findings highlight the great potential for the development of synthetic quinoxaline-1,3,4-oxadiazole hybrid derivatives as proapoptotic anticancer agents.

Synthesis and photophysical properties of selenopheno[2,3-b]quinoxaline and selenopheno[2,3-b]pyrazine heteroacenes.

In this paper, we report the novel synthesis of three different heterocycles, namely 2-arylselenopheno[2,3-b]quinoxaline, 3-(aryl/alkylselanyl)-2-arylselenopheno[2,3-b]quinoxaline and 6-phenyl-7-(arylselanyl)selenopheno[2,3-b]pyrazine derivatives, from the corresponding 2,3-dichloroquinoxaline and 2,3-dichloropyrazine derivatives. Furthermore, photophysical properties were investigated to study the effect of heteroatoms on UV-absorbance and fluorescence properties.

In situ air oxidation and photophysical studies of isoquinoline-fused N-heteroacenes.

An efficient, metal free and environment friendly synthesis of isoquinoline-fused benzimidazole has been developed via in situ air oxidation. Also, syntheses of isoquinoline-fused quinazolinone heteroacenes were successfully achieved. The synthesized isoquinoline-fused benzimidazole and isoquinoline-fused quinazolinone derivatives showed λmax, Fmax and Φf values in the ranges 356-394 nm, 403-444 nm and 0.063-0.471, respectively, in CHCl3.

Iodine mediated in situ generation of R-Se-I: application towards the construction of pyrano[4,3-b]quinoline heterocycles and fluorescence properties.

In this paper, we report the iodine mediated in situ generation of R-Se-I and further its application towards the construction of pyrano[4,3-b]quinolin-1-one derivatives. The structural elaboration of 1-chloro-8-methyl-3-phenylbenzo[b][1,6]naphthyridine 6 was successfully achieved by Sonogashira, Suzuki coupling and dehalogenation reactions. Finally, the synthesized compounds 4a, 5a, 5b, 6, and 7a-7c were studied for photophysical properties including UV-absorption, fluorescence, and quantum yield studies. The synthesized pyranoquinoline derivatives showed λmax, Fmax and Φf values in the range of 391-447 nm, 436-486 nm and 0.004-0.301, respectively in chloroform solvent.

Iron-Promoted Intramolecular Cascade Cyclization for the Synthesis of Selenophene-Fused, Quinoline-Based Heteroacenes.

Herein, we report the Fe(III)-promoted linear intramolecular cascade cyclization of 1,3-diyne and 1,3,5-triyne for the construction of selenophene-fused, quinoline-based heteroacene scaffolds. In one step, 1,3-diyne and 1,3,5-triyne were cyclized via diversified internal nucleophiles by using diorganyl diselenides. The diorganyl diselenide plays dual role, one as a cyclizing agent and second as insertion of one and/or two selenium atom and one R'-Se group in the final product. This is highly important in terms of atom economy. Diversified internal nucleophiles were used to afford quinoline- and acridine-based cores. The synthesized selenophene-fused derivatives showed λmax, Fmax, and Φf values in the range from 370-411 nm, 427-472 nm, and 0.003-0.059, respectively, in dichloromethane solvent.

Multicomponent synthesis of pyroglutamic acid derivatives via Knoevenagel-Michael-hydrolysis-lactamization-decarboxylation (KMHL-D) sequence.

A novel and practical method for the synthesis of 3-substituted pyroglutamic acid derivatives is described. One pot multicomponent reaction of Meldrum's acid, aldehyde and Schiff's base followed an unprecedented chemoselective Knoevenagel-Michael-hydrolysis-lactamization domino sequence to afford 4-carboxy 3-substituted pyroglutamic acid derivatives under mild conditions. A carboxy intermediate formed appears to accelerate its own formation. The generality of the synthesis is exemplified by the use of a wide variety of aldehydes including enolizable aliphatic aldehydes, while substrates are stable under reaction conditions.

Synthesis of thieno[2,3-b]quinoline and selenopheno[2,3-b]quinoline derivatives via iodocyclization reaction and a DFT mechanistic study.

In this letter, we report the regioselective iodocyclization reaction of 3-alkynyl-2-(methylthio)quinolines and 3-alkynyl-2-(methylseleno)quinolines for the synthesis of thieno[2,3-b]quinoline and selenopheno[2,3-b]quinoline derivatives. Furthermore, by employing various palladium-catalyzed Sonogashira, Suzuki, and Heck reactions, the structural diversification of the resulting halide derivatives, which can act as the important intermediates for building other valuable compounds, was achieved. All compounds were fully characterized by the FT-IR, mass, 1H NMR, and 13C NMR spectral data. Finally, the structure of the thieno[2,3-b]quinoline derivative was confirmed by X-ray crystallography. This methodology provided a novel pathway to access quinoline fused heterocycles via iodocyclization reaction. Furthermore, the reaction process was well elucidated by density functional theory calculations.

Synthesis, biological evaluation, and molecular docking studies of novel 3-aryl-5-(alkyl-thio)-1H-1,2,4-triazoles derivatives targeting Mycobacterium tuberculosis.

A small library of new 3-aryl-5-(alkyl-thio)-1H-1,2,4-triazoles was synthesized and screened for the antimycobacterial potency against Mycobacterium tuberculosis H37 Ra strain and Mycobacterium bovis BCG both in active and dormant stage. Among the synthesized library, 25 compounds exhibited promising anti-TB activity in the range of IC50 0.03-5.88 µg/ml for dormant stage and 20 compounds in the range of 0.03-6.96 µg/ml for active stage. Their lower toxicity (>100 µg/ml) and higher selectivity (SI = >10) against all cancer cell lines screened make them interesting compounds with potential antimycobacterial effects. Furthermore, to rationalize the observed biological activity data and to establish a structural basis for inhibition of M. tuberculosis, the molecular docking study was carried out against a potential target MTB CYP121 which revealed a significant correlation between the binding score and biological activity for these compounds. Cytotoxicity and in vivo pharmacokinetic studies suggested that 1,2,4-triazole analogues have an acceptable safety index, in vivo stability and bio-availability.

Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents.

Resistance among dormant mycobacteria leading to multidrug-resistant and extremely drug-resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives (4a-5c) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC50 ) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram-negative and Gram-positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100 µg/ml against THP-1, A549, and PANC-1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection.