Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents

Abstract

Utilizing a pharmacophore hybridization approach, we have designed and synthesized a novel series of 28 new heterobivalent β-carbolines. The in vitro cytotoxic potential of each compound was evaluated against the five cancer cell lines (LLC, BGC-823, CT-26, Bel-7402, and MCF-7) of different origin—murine and human, with the aim of determining the potency and selectivity of the compounds. Compound 8z showed antitumor activities with half-maximal inhibitory concentration (IC50) values of 9.9 ± 0.9, 8.6 ± 1.4, 6.2 ± 2.5, 9.9 ± 0.5, and 5.7 ± 1.2 µM against the tested five cancer cell lines. Moreover, the effect of compound 8z on the angiogenesis process was investigated using a chicken chorioallantoic membrane (CAM) in vivo model. At a concentration of 5 μM, compound 8z showed a positive effect on angiogenesis. The results of this study contribute to the further elucidation of the biological regulatory role of heterobivalent β-carbolines and provide helpful information on the development of vascular targeting antitumor drugs.

A pH/H2O2/MMP9 Time‐Response Gel System with Sparchigh Tregs Derived Extracellular Vesicles Promote Recovery After Acute Myocardial Infarction

“…[9] As a type dynamic covalent bond, an acylhydrazone bond is stronger than a hydrogen bond between molecules and has reversible properties under certain pH conditions (pH < 6.8) and can lead bond fracture at pH < 6.8. [26] Based on these unique properties, many studies have used acylhydrazone bonds to connect related compounds that can be separated in an acidic microenvironment (pH < 6.8). [27] The present study focused on the microenvironment of the in-…”

Anticancer agents incorporating the N‐acylhydrazone scaffold: Progress from 2017 to present

“…Except for the BGC‐823 cell line, all of the examined tumor cell lines were more sensitive to the cytotoxic effects of hydrazone with a benzyl moiety at position 9 on β‐carboline. [ 82 ]…”

Discovery of a new fungicide by screening triazole sulfonylhydrazone derivatives and its downy mildew inhibition in cucumber

“…On the other hand, hydrazones (iNHN=C‐1) are known as biologically active fragements, which are widely used as a scaffold in agricultural chemistry . It has been reported that derivatives of hydrazones are shown to possess a wide range of biological activities, such as antifungal, antibacterial, insecticidal, herbicidal, antiviral and anticancer activities . Heretofore, some pharmaceutical companies have developed dozens of fungicides, insecticides, plant growth regulators such as benquinox, hydramethylnon and diflufenzopyr .…”

“…[31][32][33] It has been reported that derivatives of hydrazones are shown to possess a wide range of biological activities, such as antifungal, antibacterial, insecticidal, herbicidal, antiviral and anticancer activities. [34][35][36][37][38][39] Heretofore, some pharmaceutical companies have developed dozens of fungicides, insecticides, plant growth regulators such as benquinox, hydramethylnon and diflufenzopyr. [40][41][42] All of the findings inspired us to design the bioactive structures with these functional motifs as potential agrochemical leads for plant disease control.…”