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. 2023 Feb 13;8(7):6669-6678.
doi: 10.1021/acsomega.2c07256. eCollection 2023 Feb 21.

Design, Synthesis, and Biological Evaluation Studies of Novel Naphthalene-Chalcone Hybrids As Antimicrobial, Anticandidal, Anticancer, and VEGFR-2 Inhibitors

Derya Osmaniye  1   2 , Begüm Nurpelin Sağlık  1   2 , Narmin Khalilova  1 , Serkan Levent  1   2 , Gizem Bayazıt  3 , Ülküye Dudu Gül  3 , Yusuf Özkay  1   2 , Zafer Asım Kaplancıklı  1
Affiliations

Design, Synthesis, and Biological Evaluation Studies of Novel Naphthalene-Chalcone Hybrids As Antimicrobial, Anticandidal, Anticancer, and VEGFR-2 Inhibitors

Derya Osmaniye et al. ACS Omega. .

Abstract

Cancer is a progressive disease that is frequently encountered worldwide. The incidence of cancer is increasing with the changing living conditions around the world. The side-effect profile of existing drugs and the resistance developing in long-term use increase the need for novel drugs. In addition, cancer patients are not resistant to bacterial and fungal infections due to the suppression of the immune system during the treatment. Rather than adding a new antibacterial or antifungal drug to the current treatment plan, the fact that the drug with anticancer activity has these effects (antibacterial and antifungal) will increase the patient's quality of life. For this purpose, in this study, a series of 10 new naphthalene-chalcone derivatives were synthesized and their anticancer-antibacterial-antifungal properties were investigated. Among the compounds, compound 2j showed activity against the A549 cell line with an IC50 = 7.835 ± 0.598 μM. This compound also has antibacterial and antifungal activity. The apoptotic potential of the compound was measured by flow cytometry and showed apoptotic activity of 14.230%. The compound also showed 58.870% mitochondrial membrane potential. Compound 2j inhibited VEGFR-2 enzyme with IC50 = 0.098 ± 0.005 μM. Molecular docking studies of the compounds were carried out by in silico methods against VEGFR-2 and caspase-3 enzymes.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Some VEGFR inhibitors.
Scheme 1
Scheme 1. Synthesis Pathway for Obtained Compounds (2a–2j)
Figure 2
Figure 2
Flow cytometric analysis quadrants of compound 2j and SD4.
Figure 3
Figure 3
Analysis of mitochondrial membrane potential of compound 2j and SD4.
Figure 4
Figure 4
Molecular docking of VEGFR-2 enzymes (PDB code: 4ASE and PDB Code: 4ASD) and Caspase-3 enzyme (PDB code: 4QTX) with compound 2j. (A) The three-dimensional interacting mode of compound 2j in the active region of VEGFR-2 enzyme (PDB ID: 4ASE). (B) 3D docking pose of compound 2j with the key amino acids within the binding pocket of 4ASE is shown: aromatic hydrogen bonds with blue dashed lines, hydrogen bonds with yellow dashed lines, and salt bridge with purple dashed lines. (C) The three-dimensional interacting mode of compound 2j in the active region of VEGFR-2 enzyme (PDB ID: 4ASD). (D) 3D docking pose of compound 2j with the key amino acids within the binding pocket of 4ASD is shown: aromatic hydrogen bonds with blue dashed lines, hydrogen bonds with yellow dashed lines, and salt bridge with purple dashed lines. (E) The three-dimensional interacting mode of compound 2j in the active region of Caspase-3 enzyme (PDB ID: 4QTX). (F) 3D docking pose of compound 2j with the key amino acids within the binding pocket of 4QTX is shown: aromatic hydrogen bonds with blue dashed lines, hydrogen bonds with yellow dashed lines and cation–pi interaction with dark green dashed lines, pi–pi interaction with green dashed lines.
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