Sulfonylated Indeno[1,2-]quinoline Derivatives as Potent EGFR Tyrosine Kinase Inhibitors.

The epidermal growth factor receptor (EGFR) has been considered a potential target for lung cancer therapy due to its essential role in regulating the survival and proliferation of cancer cells. Although erlotinib, a potent EGFR tyrosine kinase (EGFR-TK) inhibitor, has been used as the first-line drug for lung cancer treatment, acquired drug resistance caused by the T790M secondary mutation of EGFR-TK inevitably develops after a median response duration of 9-13 months. Thus, the search for promising compounds to effectively target EGFR-TK has become an imperative necessity.

Unraveling the photophysical characteristics and biological applications of vinyl sulfones as viscosity sensors.

For the first time, a series of vinyl sulfone-NH-based push-pull fluorophores (4a-4d) were introduced for their potential use in biological applications. The fluorophores 4a-4d were readily synthesized upon reduction of the corresponding vinyl sulfones-NO (3a-3d), which were prepared by sulfonylation of nitrostyrene. Both types of probes can be prepared in high yields through a few steps with minimal cost.

Quinoline-Malononitrile-Based Aggregation-Induced Emission Probe for Monoamine Oxidase Detection in Living Cells.

A quinoline-malononitrile (QM)-based aggregation-induced emission probe was developed to detect MAOs in cells through an enzymatic reaction followed by β-elimination. After being incubated at 37 °C, responded to the MAO enzymes with great specificity and within just 5 min. This 5 min responsive mechanism was fast, with the limit of detection (LOD) at 5.

Identification of Vinyl Sulfone Derivatives as EGFR Tyrosine Kinase Inhibitor: In Vitro and In Silico Studies.

Epidermal growth factor receptor (EGFR), overexpressed in many types of cancer, has been proved as a high potential target for targeted cancer therapy due to its role in regulating proliferation and survival of cancer cells. In the present study, a series of designed vinyl sulfone derivatives was screened against EGFR tyrosine kinase (EGFR-TK) using in silico and in vitro studies. The molecular docking results suggested that, among 78 vinyl sulfones, there were eight compounds that could interact well with the EGFR-TK at the ATP-binding site.

Molecular dynamics simulations of sulfone derivatives in complex with DNA topoisomerase IIα ATPase domain.

Human topoisomerase II alpha (TopoIIα) is a crucial enzyme involved in maintaining genomic integrity during the process of DNA replication and mitotic division. It is a vital therapeutic target for designing novel anticancer agents in targeted cancer therapy. Sulfones, members of organosulfur compounds, have been reported to possess various biological activities such as antimicrobial, anti-inflammatory, anti-HIV, anticancer, and antimalarial properties.

Alkanethiol-Mediated Cyclization of -Alkynylisocyanobenzenes: Synthesis of Bis-Thiolated Indole Derivatives.

Reactions of -alkynylisocyanobenzenes with a variety of alkanethiols (Alk-SH) provide the corresponding bis-thiolated indole derivatives. The advantages of the reaction include metal-free, room-temperature, mild reaction conditions and broad functional group compatibility. The reaction proceeds via nucleophilic addition of an alkanethiol to an isonitrile moiety, 5- cyclization, followed by nucleophilic addition of an alkanethiol to a 3-alkylidene indole intermediate.

Synthesis of Indolo- and Benzothieno[2,3-]quinolines by a Cascade Cyclization of -Alkynylisocyanobenzene Derivatives.

A new synthetic approach for the synthesis of indolo[2,3-]quinolines and benzothieno[2,3-]quinolines has been developed by employing the freshly prepared -alkynylisocyanobenzenes derived from -alkynylformamide derivatives as substrates. The synthetic transformations involved chloride-ion-triggered 6- cyclization of -alkynylisocyanobenzenes to generate 2-chloroquinolines in situ, which further cyclized intramolecularly with nitrogen or sulfur atom via a cascade process to provide the corresponding indolo[2,3-]quinolines and benzothieno[2,3-]quinolines, respectively, in moderate to excellent yields.

Sulfinates and thiocyanates triggered 6-endo cyclization of o-alkynylisocyanobenzenes.

Diverse 2-sulfonyl- and 2-thiocyanato-3-substituted quinolines were synthesized from o-alkynylisocyanobenzenes by nucleophilic addition of the respective sulfinate sodium salts and ammonium thiocyanate to the isocyanide moiety followed by cyclization. The salient features of the methodology include metal-free, ambient temperature and mild reaction conditions, ease of reagent handling, and broad functional group tolerance.

Synthesis of 3-substituted quinolin-2(1H)-ones via the cyclization of o-alkynylisocyanobenzenes.

A facile synthesis of various functionalized 3-substituted quinolin-2(1H)-ones through Ag(i) nitrate-catalyzed cyclization of o-alkynylisocyanobenzenes is described. The reaction allows rapid and convenient access to 3-substituted quinolin-2(1H)-one scaffolds in moderate to good yields.