Cheminformatics-based design and biomedical applications of a new Hydroxyphenylcalix[4] resorcinarene as anti-cancer agent

S F Alshahateet; R M Altarawneh; S A Al-Trawneh; Y M Al-Saraireh; W M Al-Tawarh; K R Abuawad; Y M Abuhalaweh; M Zerrouk; A Ait Mansour; R Salghi; B Hammouti; M Merzouki; R Sabbahi; L Rhazi; Mohammed M Alanazi; K Azzaoui

doi:10.1038/s41598-024-82115-1

Cheminformatics-based design and biomedical applications of a new Hydroxyphenylcalix[4] resorcinarene as anti-cancer agent

Sci Rep. 2024 Dec 13;14(1):30460. doi: 10.1038/s41598-024-82115-1.

Authors

S F Alshahateet¹, R M Altarawneh², S A Al-Trawneh², Y M Al-Saraireh³, W M Al-Tawarh², K R Abuawad³, Y M Abuhalaweh³, M Zerrouk⁴, A Ait Mansour⁵, R Salghi⁵, B Hammouti^{6

7}, M Merzouki⁸, R Sabbahi⁹, L Rhazi¹⁰, Mohammed M Alanazi¹¹, K Azzaoui⁴

Affiliations

¹ Department of Chemistry, Faculty of Science, Mutah University, P.O. Box 7, Al-Karak, 61710, Jordan. [email protected].
² Department of Chemistry, Faculty of Science, Mutah University, P.O. Box 7, Al-Karak, 61710, Jordan.
³ Department of Pharmacology, Faculty of Medicine, Mutah University, P.O. Box 7, Al-Karak, 61710, Jordan.
⁴ Engineering Laboratory of Organometallic, Molecular Materials and Environment, Faculty of Sciences, Sidi Mohammed Ben Abdellah University, 30000, Fez, Morocco.
⁵ Laboratory of Applied Chemistry and Environment, ENSA, University Ibn Zohr, P.O. Box 1136, 80000, Agadir, Morocco.
⁶ Euromed Research Center, Euromed Polytechnic School, Euromed University of Fes, UEMF, 30030, Fez, Morocco.
⁷ Laboratory of Industrial Engineering, Energy and the Environment (LI3E) SUPMTI, Rabat, Morocco.
⁸ Laboratory of Applied Chemistry and Environment, Department of Chemistry, Faculty of Sciences, Mohammed 1st University, Oujda, Morocco.
⁹ Research Team in Science and Technology, Higher School of Technology, Ibn Zohr University, P.O. Box 3007, Laayoune, Morocco.
¹⁰ Institut Polytechnique UniLaSalle, Université d'Artois, ULR 7519, 19 Rue Pierre Waguet, BP 30313, 60026, Beauvais, France.
¹¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, 11451, Riyadh, Saudi Arabia. [email protected].

Abstract

The distinct conformational characteristics, functionality, affordability, low toxicity, and usefulness make calixarene-based compounds a promising treatment option for cancer. The aim of the present study is to synthesize a new calixarene-based compound and assess of its anticancer potential on some human cancer cells. The synthesized C-4-Hydroxyphenylcalix[4] resorcinarene (HPCR) was characterized by several spectroscopic techniques such as 1HNMR, 13CNMR, and X-ray crystallographic analysis to confirm its purity and identity. IC₅₀ values were identified for cancer cell lines (U-87, MCF-7, A549) and human dermal fibroblasts cell line (HDF) after treatment with HPCR and the standard drug Cisplatin. A significant selective growth inhibitory activity against U-87 and A549 cell lines was obtained at an HPCR concentration of 100 μM. The MOE docking module (version 2015) was utilized to assess the extent of inhibition for HPCR compound against four cancer-related proteins (3RJ3, 7AXD, 6DUK, and 1CGL).

Keywords: Anti-cancer agent; Anti-proliferative activity; Calix[n]arenes; MTT assay; Molecular docking.

MeSH terms

A549 Cells
Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Calixarenes* / chemistry
Calixarenes* / pharmacology
Cell Line, Tumor
Cell Proliferation / drug effects
Cheminformatics / methods
Crystallography, X-Ray
Drug Design
Drug Screening Assays, Antitumor
Humans
MCF-7 Cells
Molecular Docking Simulation*
Phenylalanine* / analogs & derivatives
Phenylalanine* / chemistry
Phenylalanine* / pharmacology

Substances

Calixarenes
Antineoplastic Agents
Phenylalanine
resorcinarene

Abstract

MeSH terms

Substances

Grants and funding