2. Academic Validation
  3. In silico, in vitro VEGFR-2 inhibition, and anticancer activity of a 3-(hydrazonomethyl)naphthalene-2-ol derivative

In silico, in vitro VEGFR-2 inhibition, and anticancer activity of a 3-(hydrazonomethyl)naphthalene-2-ol derivative

  • J Biomol Struct Dyn. 2023 Sep-Oct;41(16):7986-8001. doi: 10.1080/07391102.2022.2127907.
Eslam B Elkaeed 1,  Reda G Yousef 2,  Hazem Elkady 2,  Ahmed B M Mehany 3,  Bshra A Alsfouk 4,  Dalal Z Husein 5,  Ibrahim M Ibrahim 6,  Ahmed M Metwaly 7 8,  Ibrahim H Eissa 2
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, Saudi Arabia.
  • 2 Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.
  • 3 Zoology Department, Faculty of Science (Boys), Al-Azhar University, Cairo, Egypt.
  • 4 Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
  • 5 Chemistry Department, Faculty of Science, New Valley University, El-Kharja, Egypt.
  • 6 Biophysics Department, Faculty of Science, Cairo University, Cairo, Egypt.
  • 7 Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.
  • 8 Biopharmaceutical Products Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria, Egypt.
PMID: 36184591 DOI: 10.1080/07391102.2022.2127907
Abstract

In agreement with the general features of VEGFR-2 inhibitors, a new naphthalene analog (compound 7) has been designed and synthesized. The inhibitory potential of compound 7 was indicated by the proper binding and the perfect energy of -21.10 kcal/mol compared to sorafenib (-21.22) in the molecular docking studies. Next, six MD simulation studies over 100 ns (RMSD, RMSF, SASA, RoG, hydrogen bonding, and distance between the center of mass) confirmed the accurate interaction of compound 7 with the catalytic pocket of VEGFR-2. Similarly, an MM-GBSA established proper binding showing an exact total binding energy of -36.95 ± 3.03 kcal/Mol. Additionally, the MM-GBSA experiment indicated the vital Amino acids in the binding process. Types and number of interactions of compound 7 with catalytic pocket of VEGFR-2 were determined through Protein-Ligand Interaction Profiler (PLIP). As a new compound, the DFT was employed to optimize the molecular structure of compound 7. The DFT experiments also verified the interaction features of compound 7 with the VEGFR-2 active site. In silico ADMET experiments revealed the general drug-likeness of compound 7. Fascinatingly, the in vitro examinations were consistent with the in silico experiments as compound 7 inhibited the VEGFR-2 Enzyme with an IC50 value of 37 nM. Captivatingly, compound 7 inhibited both MCF-7 and HCT 116 Cancer cells exhibiting IC50 values of 10.56 and 7.07 µM exhibiting excellent selectivity indexes of 9.04 and 13.50, respectively.Communicated by Ramaswamy H. Sarma.

Keywords

ADMET; DFT; MD simulations; MM-GBSA; Naphthalene; VEGFR-2 inhibitor; docking; in vitro cytotoxicity.

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