Design, Synthesis, and Evaluation of Novel Indole Hybrid Chalcones and Their Antiproliferative and Antioxidant Activity

Abstract

The synthesis, anticancer, and antioxidant activities of a series of indole-derived hybrid chalcones are reported here. First, using the well-known Claisen–Schmidt condensation method, a set of 29 chalcones has been designed, synthesized, and consequently characterized. Subsequently, screening for the antiproliferative activity of the synthesized hybrid chalcones was performed on five cancer cell lines (HCT116, HeLa, Jurkat, MDA-MB-231, and MCF7) and two non-cancer cell lines (MCF-10A and Bj-5ta). Chalcone 18c, bearing 1-methoxyindole and catechol structural features, exhibited selective activity against cancer cell lines with IC50 values of 8.0 ± 1.4 µM (Jurkat) and 18.2 ± 2.9 µM (HCT116) and showed no toxicity to non-cancer cells. Furthermore, antioxidant activity was evaluated using three different methods. The in vitro studies of radical scavenging activity utilizing DPPH radicals as well as the FRAP method demonstrated the strong activity of catechol derivatives 18a–c. According to the ABTS radical scavenging assay, the 3-methoxy-4-hydroxy-substituted chalcones 19a–c were slightly more favorable. In general, a series of 3,4-dihydroxychalcone derivatives showed properties as a lead compound for both antioxidant and antiproliferative activity.

Syntheses, reactivity, and biological applications of coumarins

“…The process proceeded via a tandem cyclization reaction of phenylglyoxal derivatives ( 21 ) and several substituted anilines ( 22 ) in a multicomponent approach in the presence of the Brønsted acidic ionic liquid [BSMIM]OTs ( 24 , 1-butane sulfonic acid-3-methylimidazolium tosylate) as a green catalyst in refluxing ethanol. Considering the emerging importance of indole scaffold endowed with antitumor, antiviral and antifungal effects ( Citarella et al, 2023 ; Jagadeesan and Karpagam, 2023 ; Kudličková et al, 2023 ), the authors decided to screen the library of 3-indole coumarins ( 26 ) in silico for their ability to bind key proteins in tumorigenesis revealing interesting outcomes, which was confirmed also by a preliminary bioactivity evaluation.…”

In Vitro and In Vivo Biological Evaluation of Indole-thiazolidine-2,4-dione Derivatives as Tyrosinase Inhibitors

“…Indole scaffold with a structure of pyrrole in parallel with benzene has been one of the key structural nuclei in drug development due to its rich pharmacological activity and specific property of imitating peptide structure to bind with enzymes [22][23][24][25][26]. Previous studies have reported some indole derivatives as potential tyrosinase inhibitors.…”

“…Previous studies have reported some indole derivatives as potential tyrosinase inhibitors. For example, the Mirfazli group introduced carbohydrazide into an indole scaffold to obtain substituted indole-carbohydrazides (Figure 1A), which presented excellent tyrosinase inhibitory activity [24]. The Abbasi group also synthesized the indole-N-ethyltriazole hybrids amalgamated with N-arylated ethanamides (Figure 1B) as tyrosinase inhibitors [25].…”

“…sinase inhibitory activity [24]. The Abbasi group also synthesized the indole-N-ethyltriazole hybrids amalgamated with N-arylated ethanamides (Figure 1B) as tyrosinase inhibitors [25].…”

Synthesis, Antimicrobial and Antibiofilm Activities, and Molecular Docking Investigations of 2-(1H-Indol-3-yl)-1H-benzo[d]imidazole Derivatives

“…Tecastemizole (Norastemizole) shows anti-inflammatory activity [14]. It is worth noting that indole derivatives exhibit a wide range of biological activities [15]: antiproliferative, antioxidant [16], antiviral [17], antibacterial, and antifungal [18]. The combination of a benzimidazole moiety with an additional azaheterocycle in a single molecule may promise a synergistic enhancement of therapeutic effect.…”