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. 2024 Jul 26;14(32):23495-23504.
doi: 10.1039/d4ra03963g. eCollection 2024 Jul 19.

Synthesis, characterization and biological research of novel 2-(quinoline-4-carbonyl)hydrazide-acrylamide hybrids as potential anticancer agents on MCF-7 breast carcinoma cells by targeting EGFR-TK

Hany M Abd El-Lateef  1   2 , Duaa Bafail  3 , Noura Hamdi Yousef Alhalees  4 , Eslam E M Toson  5 , Ali H Abu Almaaty  6 , Elsherbiny H Elsayed  5 , Islam Zaki  7 , Magdy M Youssef  8
Affiliations

Synthesis, characterization and biological research of novel 2-(quinoline-4-carbonyl)hydrazide-acrylamide hybrids as potential anticancer agents on MCF-7 breast carcinoma cells by targeting EGFR-TK

Hany M Abd El-Lateef et al. RSC Adv. .

Abstract

Novel derivatives of the 2-(quinoline-4-carbonyl)hydrazide scaffold carrying the acrylamide moiety were synthesized and tested for their cytotoxic efficacy against the breast carcinoma MCF-7 cell line. The most active members 6a, 6b and 6h revealed significant antiproliferative action with an IC50 value of 3.39, 5.94 and 2.71 μM, respectively, which were more potent than the reference drug Dox (IC50 = 6.18 μM). Aiming to enlighten the antiproliferative activity, compounds 6a and 6h were examined for their inhibitory potential against EGFR kinase. The results demonstrated that compound 6h displayed potent inhibitory activity, as concluded from the IC50 value (IC50 = 0.22 μM) compared to the standard drug Lapatinib (IC50 value of 0.18 μM). Compound 6h was found to induce significant cellular cycle arrest at the G1 phase and provoke apoptosis. Besides, compound 6h triggered apoptosis via upregulating p53 and initiator caspase 9 by 7.4- and 8.7-fold, respectively, compared to DMSO controls.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Fig. 1
Fig. 1. The design concept used for the synthesis of the title compounds 5 and 6a–i.
Scheme 1
Scheme 1. Synthesis of the target 2-(quinoline-4-carbonyl)hydrazide-acrylamide hybrids 5 and 6a–i. Reagents: (i) 4-Br-C6H4COCH3, 33% KOH, C2H5OH, reflux 12 h; (ii) C2H5OH, Conc. H2SO4, reflux 12 h; (iii) NH2NH2, C2H5OH, reflux 7 h; (iv) respective 2-(4-methoxybenzamido)carboxylate, NaOAc, C2H5OH, reflux 18 h.
Fig. 2
Fig. 2. Results of EGFR-TK inhibition test as IC50 result (μM) of tested 2-(quinoline-4-carbonyl)hydrazide-acrylamide derivatives 6a, 6h and lapatinib.
Fig. 3
Fig. 3. 2-(Quinoline-4-carbonyl)hydrazide-3-(4-nitrophenyl)acrylamide 6h alters cellular cycle distribution in MCF-7 cells treated with 2.71 μM of compound 6h and compared to DMSO controls.
Fig. 4
Fig. 4. 2-(Quinoline-4-carbonyl)hydrazide-3-(4-nitrophenyl)acrylamide 6h provoke apoptotic process in the examined MCF-7 cells after treatment with 2.71 μM of compound 6h and compared to DMSO controls.
Fig. 5
Fig. 5. 2-(Quinoline-4-carbonyl)hydrazide-3-(4-nitrophenyl)acrylamide 6h mediate p53 and caspase 9 expression. MCF-7 cells were treated with 2.71 μM of tested hybrid for 48 h before qRT-PCR measurement and compared to untreated controls. (A) p53 level; (B) caspase 9 level.
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