Benzofuran hydrazones as potential scaffold in the development of multifunctional drugs: Synthesis and evaluation of antioxidant, photoprotective and antiproliferative activity

Abstract

New benzofuranhydrazones 3-12 were easily prepared and assayed for their radical-scavenging ability. Hydrazones 3-12 showed different extent antioxidant activity in DPPH, FRAP and ORAC assays. Good antioxidant activity is related to the number and position of hydroxyl groups on the arylidene moiety. High antioxidant activity is showed by the 2-hydroxy-4-(diethylamino)benzylidene derivative 11. Furthermore, hydrazones 3-12 showed photoprotective capacities with satisfactory in vitro SPF as compared to the commercial PBSA sunscreen filter. The antiproliferative effects of the hydrazones 3-12 was tested on erythroleukemia K562 and Colo-38 melanoma human cells. All the compounds showed growth inhibition in the micromolar to sub micromolar concentration range. If taken together these results points to benzofuran hydrazones as potential multifunctional molecules especially in the treatment of neoplastic diseases being the good antioxidant properties of 5, 7 and 11 correlated to their high antiproliferative activity.

In-Vitro Evaluation of Antioxidant, Antiproliferative and Photo-Protective Activities of Benzimidazolehydrazone Derivatives

“…On the other hand, also hydrazone moieties are endowed with potent antioxidant potency [20][21][22][23]. Based on these findings and as a continuation of our works on antioxidant agents [24][25][26], here we report and discuss the antioxidant properties of benzimidazolehydrazones containing a phenolic group and their structure-activity relationships (SAR). The studied molecules have been synthesized and chemically characterized by us during a previous synthetic study [27], but not fully investigated for their activity.…”

“…Research aimed at the development of multifunctional molecules has been at the center of our work for years [24,25,27] and has led us to investigate different scaffolds such as benzimidazole, benzofurane and indole nuclei, which are however connected by an hydrazone linker and an aromatic nucleus, differently substituted, considering the importance of fractions suitable to extend the conjugation to the aromatic ring. All the derivatives have been tested for their potential antioxidant, UV filtering and anti-proliferative activity (in particular against melanoma cells).…”

“…The study of benzofuran derivatives [24] revealed a correlation between the number and position of hydroxyl groups on the arylidene portion and good antioxidant capacity. A high activity had instead been found for the 2-hydroxy-4-(diethylamino)benzylidene derivative.…”

“…The benzimidazole hydrazones 3-15 were tested against DPPH• radical following the Wang et al method [33] modified as previously reported [24]. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging assay measures the hydrogen donation ability of an antioxidant to convert the stable DPPH free radical into 1,1-diphenyl-2-picrylhydrazyl.…”

Benzofuran–isatin Hybrids: Design, Synthesis, and In Vitro Anti‐cancer Activities

“…Benzofuran and isatin (indoline‐2,3‐dione) derivatives possess a variety of biological properties such as anti‐bacterial , anti‐tubercular , and anti‐malarial activities, which occupy an important position in the development of new drugs. Benzofuran and isatin derivatives also exhibit promising anti‐cancer activities , and some of them such as semaxanib (Fig. ) are under clinical trials or have already been used in clinics for the treatment of various cancers .…”