High pressure assisted synthetic approach for novel 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline derivatives and their assessment as anticancer agents

Abstract

A novel, expedient and effective methodology for the synthesis of distinctly substituted 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline systems has been developed with a new synthetic platform. This process includes ammonium acetate-mediated cyclocondensation reactions of 3-oxo-2-arylhydrazonopropanals with benzosuberone and tetralone precursors, respectively, using the high-pressure Q-tube reactor, which has been found to be superior to both conventional heating and microwave irradiation. The novel protocol benefits from its high atom efficiency, economy, ease of workup, broad substrate scope and is also applicable to gram-scale synthesis. To identify and confirm the newly synthesized targeted compounds, the X-ray single-crystal as well as all possible spectroscopic methods were utilized. The cytotoxicity of the newly synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a–j and 5,6-dihydrobenzo-[h]quinolines derivatives 6a–e were preliminary examined toward three cell lines of human cancer; lung cancer (A549), breast cancer (MCF-7) and colon cancer (HCT-116), by applying the MTT colorimetric assay. The achieved results reflected the promising profile of the prepared compounds in this study against cancer cells and have shown that members from the synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a–j exhibited promising cytotoxicity’s against MCF-7, and A549 cancer cells respectively, while the HCT-116 (colon) cancer cells were inhibited by certain examples of 5,6-dihydrobenzo[h]quinoline derivatives 6c,d. These promising results could serve as a good primary base for further research into the design of anticancer drugs.

High-Pressure Metal-Free Catalyzed One-Pot Two-Component Synthetic Approach for New 5-Arylazopyrazolo[3,4-b]Pyridine Derivatives

“…To achieve this target, a diversity of 3-oxo-arylhydrazonals 2a – v was prepared and introduced in order to evaluate their reactions with 5-amino-2-phenyl-4 H -pyrazol-3-one ( 1 ) under the specified optimal conditions ( Table 1 , entry 12). In general, the electronic properties of the aryl motifs attached to 3-oxo-arylhydrazonals ( 2 ) had a minimal influence on reaction efficacy [ 28 , 29 ]. The reaction was exceptionally adaptable to both electron-releasing motifs as well as the electron-accepting motifs.…”

Green Protocol for the Novel Synthesis of Thiochromeno[4,3-b]pyridine and Chromeno[4,3-b]pyridine Derivatives Utilizing a High-Pressure System

“…A little attention has been paid toward the biologically active thiochromeno­[2,3- b ]­pyridine derivatives , where few synthetic routes for some examples of thiochromeno­[2,3- b ]­pyridines were published. − Apart from this, only one publication for the synthesis of the thiochromeno­[4,3- b ]­pyridine skeleton was reported via a multicomponent reaction of thiochromanone with dimethylformamide-dimethylacetal and ethyl acetoacetate in the presence of ammonium acetate . In continuation to our work which aimed at developing new synthetic routes for new heterocyclic compounds, − herein the Q-tube reactor was used in this study. In comparison with conventional heating, the Q-tube reactor has several characteristics and features − including (1) better yield and performance, (2) a cleaner product profile that means light color and less impurities and byproducts, (3) energy savings, lower reaction time, and higher reproducibility, and (4) cheaper and safer because the sealing and pressing are easy.…”

Anticancer therapeutic potential of benzofuran scaffolds

“…23,24 Recently, our research interest was focused on the biological applications of benzofuran derivatives and other heterocycles of potent anticancer activities. [25][26][27][28][29] Herein, we report an updated comprehensive outlines of the recent developments (2019-2022) of the anticancer potentiality of both natural and synthetic bioactive benzofuran-based compounds as a highly signicant source for drug development and discovery.…”