BTEAC Catalyzed Ultrasonic-Assisted Synthesis of Bromobenzofuran-Oxadiazoles: Unravelling Anti-HepG-2 Cancer Therapeutic Potential through In Vitro and In Silico Studies
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Published:2023-02-03
Issue:3
Volume:24
Page:3008
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Irfan Ali1ORCID, Zahoor Ameer Fawad1ORCID, Rasul Azhar2ORCID, Al-Hussain Sami A.3, Faisal Shah4ORCID, Ahmad Sajjad5ORCID, Noor Rida1, Muhammed Muhammed Tilahun6ORCID, Zaki Magdi E. A.3ORCID
Affiliation:
1. Department of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan 2. Department of Zoology, Government College University Faisalabad, Faisalabad 38000, Pakistan 3. Department of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia 4. Department of Chemistry, Islamia College University Peshawar, Peshawar 25120, Pakistan 5. Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan 6. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Suleyman Demirel University, Isparta 32260, Turkey
Abstract
In this work, BTEAC (benzyl triethylammonium chloride) was employed as a phase transfer catalyst in an improved synthesis (up to 88% yield) of S-alkylated bromobenzofuran-oxadiazole scaffolds BF1-9. These bromobenzofuran-oxadiazole structural hybrids BF1-9 were evaluated in vitro against anti-hepatocellular cancer (HepG2) cell line as well as for their in silico therapeutic potential against six key cancer targets, such as EGFR, PI3K, mTOR, GSK-3β, AKT, and Tubulin polymerization enzymes. Bromobenzofuran structural motifs BF-2, BF-5, and BF-6 displayed the best anti-cancer potential and with the least cell viabilities (12.72 ± 2.23%, 10.41 ± 0.66%, and 13.08 ± 1.08%), respectively, against HepG2 liver cancer cell line, and they also showed excellent molecular docking scores against EGFR, PI3K, mTOR, and Tubulin polymerization enzymes, which are major cancer targets. Bromobenzofuran-oxadiazoles BF-2, BF-5, and BF-6 displayed excellent binding affinities with the active sites of EGFR, PI3K, mTOR, and Tubulin polymerization enzymes in the molecular docking studies as well as in MMGBSA and MM-PBSA studies. The stable bindings of these structural hybrids BF-2, BF-5, and BF-6 with the enzyme targets EGFR and PI3K were further confirmed by molecular dynamic simulations. These investigations revealed that 2,5-dimethoxy-based bromobenzofuran-oxadiazole BF-5 (10.41 ± 0.66% cell viability) exhibited excellent cytotoxic therapeutic efficacy. Moreover, computational studies also suggested that the EGFR, PI3K, mTOR, and Tubulin polymerization enzymes were the probable targets of this BF-5 scaffold. In silico approaches, such as molecular docking, molecular dynamics simulations, and DFT studies, displayed excellent association with the experimental biological data of bromobenzofuran-oxadiazoles BF1-9. Thus, in silico and in vitro results anticipate that the synthesized bromobenzofuran-oxadiazole hybrid BF-5 possesses prominent anti-liver cancer inhibitory effects and can be used as lead for further investigation for anti-HepG2 liver cancer therapy.
Funder
Deanship of Scientific Research, Imam Mohammad Ibn Saud Islamic University (IMSIU), Saudi Arabia
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Cited by
5 articles.
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