Design, Synthesis and Biological Evaluation of Benzohydrazide Derivatives Containing Dihydropyrazoles as Potential EGFR Kinase Inhibitors

Abstract

A series of novel benzohydrazide derivatives containing dihydropyrazoles have been synthesized as potential epidermal growth factor receptor (EGFR) kinase inhibitors and their biological activities as potential antiproliferative agents have been evaluated. Among these compounds, compound H20 exhibited the most potent antiproliferative activity against four cancer cell line variants (A549, MCF-7, HeLa, HepG2) with IC 50 values of 0.46, 0.29, 0.15 and 0.21 µM respectively, which showed the most potent EGFR inhibition activities (IC 50 = 0.08 µM for EGFR). Molecular modeling simulation studies were performed in order to predict the biological activity and activity relationship (SAR) of these benzohydrazide derivatives. These results suggested that compound H20 may be a promising anticancer agent.

RETRACTED: Design, Synthesis, and Biological Evaluation of (E)-N'-((1-Chloro-3,4-Dihydronaphthalen-2-yl)Methylene)Benzohydrazide Derivatives as Anti-prostate Cancer Agents

“…In vitro anticancer activity of the synthesized hydrazide derivatives was determined against human colorectal (HCT116) cancer cells line. Recently, hydrazide derivative was reported as a potent and selective inhibitor for antibacterial–antifungal (Somashekhar, 2013; Popiołek, 2017), anti-inflammatory (Todeschini et al, 1998), antimalarial (Melnyk et al, 2006), and anti-tuberculosis activities (Bedia et al, 2006), as an Entamoeba histolyica (Afreen et al, 2016), a cruzipain inhibitor (Cerecetto and Gonzalez, 2010) and as Epidermal growth factor receptor (EGFR) Kinase Inhibitor (Wang et al, 2016). Thus, benzohydrazides are important moieties that exhibit more effective inhibitory activity against various cancer cell lines such as A549, MCF-7, HeLa, and HepG2 (Wang et al, 2016).…”

Antimicrobial, Antioxidant, and Anticancer Activities of Some Novel Isoxazole Ring Containing Chalcone and Dihydropyrazole Derivatives

“…Chalcones exhibited excellent antibacterial potency whereas the dihydropyrazoles showed tremendous antifungal activity compared to the standard drugs ciprofloxacin and fluconazole. (25). However, these compounds had lower activity than the standard drugs.…”

“…In the chalcone monosubstituted series (17, 18, and 19), substituting at positions 2 or 4 or 6 on the phenyl ring did not improve the antioxidant activity. In the disubstituted series (20)(21)(22)(23)(24)(25), compound 25 with substitutions at position 3 and 5 on the phenyl ring gave the highest activity of 9 µg/mL. In the trisubstituted series (26)(27)(28)(29)(30)(31), substitutions at positions 2, 4, and 6 resulted in the highest IC 50 of 5 µg/mL among all the series.…”

“…The synthesis and characterization of compounds 17-31 and 32-46 has been published previously [9,11]. Chalcones (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) were prepared by Claisen-Schmidt condensation reaction (Scheme 1) in the presence of aqueous potassium hydroxide as a catalyst. The 1-(isoxazole-5-yl)ethanone (1) was condensed with substituted benzaldehyde (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) under basis conditions at room temperature for 24 h. The reaction was stopped by transferring the mixture on ice.…”

“…Hence, we decided to screen our compounds for antibacterial, antifungal, antioxidant, and anticancer (prostrate cell line) activities. The target chalcones (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) and pyrazolines (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) were tested for their antimicrobial activities by serial tube dilution method against two types of bacterial and fungal strains (Tables 1 and 2). The bacterial strains used for the testing, including Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, whereas the fungal strains employed were Aspergillus niger and Candida tropicalis.…”