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Integrating N-alkyl amide in the chalcone framework: synthesis and evaluation of its anti-proliferative potential against AGS cancer cell line

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Abstract

On the basis of the urgent need to develop innovative and safe anticancer compounds, a series of chalcones, functionalized with various substituents in the aromatic portions and a long N-alkyl amide moiety, were designed and synthesized. The compatibility of novel compounds was firstly evaluated on non-tumoral human gingival fibroblasts (HGFs), secondly, the anti-proliferative effect on an adenocarcinoma gastric cell line (AGS) was measured. Among the chalcones, compound 3, at 50 µM after 48 and 72 h, showed, at the same time, an appreciable capability to counteract tumoral AGS viability and to preserve a high rate of healthy HGFs viability. Cell cycle analysis, performed on AGS cell line with 3 subtoxic dose (30 µM), suggested that the anti-proliferative effect could be related to a cell cycle arrest during the first stage and to an increase in the oxidative stress demonstrated by the significant augmentation of Reactive Oxygen Species release. Collectively, we have demonstrated that chalcone 3 had a potent anti-proliferative potential for the treatment of gastric adenocarcinoma and could be further investigated for new drug development.

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Funding

This research received intramural grants from “G. d’Annunzio” University to S.C. (FAR2021).

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Author notes

  1. Rinshana Fathima Abdul Azeez and Susi Zara have contributed equally.

Authors and Affiliations

  1. Centre for Experimental Drug Design and Development, Department of Pharmaceutical Chemistry, Al-Shifa College of Pharmacy, Perinthalmanna, Kerala, 679325, India

    Rinshana Fathima Abdul Azeez, Sanal Dev, Ajeesh Vengamthodi, Fathima Sahla Kavully, Raihan Arikkattel Abdu & Kadeeja Thottungal Kalathil

  2. Department of Pharmacy, “G. d’Annunzio” University of Chieti-Pescara, Chieti, Italy

    Susi Zara, Alessia Ricci & Simone Carradori

  3. Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, 72341, Al Jouf, Saudi Arabia

    Mohamed A. Abdelgawad

  4. Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, 682041, India

    Bijo Mathew

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  1. Rinshana Fathima Abdul Azeez
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Contributions

All authors reviewed the manuscript. SC and BM conceived the study, provided funding and wrote the paper; S.Z. and A.R. performed the biological evaluation; RFAA, SD, AV, FSK, RAA, KTK and MAA synthesized and characterized the compounds.

Corresponding authors

Correspondence to Sanal Dev, Bijo Mathew or Simone Carradori.

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Azeez, R.F.A., Zara, S., Ricci, A. et al. Integrating N-alkyl amide in the chalcone framework: synthesis and evaluation of its anti-proliferative potential against AGS cancer cell line. Res Chem Intermed 49, 203–220 (2023). https://doi.org/10.1007/s11164-022-04864-w

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