2. Academic Validation
  3. Unveiling the anticancer potential of novel spirooxindole-tethered pyrazolopyridine derivatives

Unveiling the anticancer potential of novel spirooxindole-tethered pyrazolopyridine derivatives

  • Bioorg Chem. 2024 Aug 31:153:107778. doi: 10.1016/j.bioorg.2024.107778.
Wagdy M Eldehna 1,  Maha-Hamadien Abdulla 2,  Mohamed S Nafie 3,  Ahmed E Elsawi 4,  Salsabil Ayman 5,  Mai I Shahin 6,  Noura S Alhassan 7,  Ahmad M Zubaidi 7,  Hazem A Ghabbour 8,  Mahmoud Elaasser 9,  Ahmed A Al-Karmalawy 10,  Hatem A Abdel-Aziz 11
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, P.O. Box 33516, Kafrelsheikh, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia St., Alexandria 21648, Egypt. Electronic address: wagdy2000@gmail.com.
  • 2 Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia. Electronic address: mabdulla@ksu.edu.sa.
  • 3 Department of Chemistry, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; Chemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt.
  • 4 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, P.O. Box 33516, Kafrelsheikh, Egypt. Electronic address: phd.ahmed.elsawi@gmail.com.
  • 5 Scientific Research and Innovation Support Unit, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt.
  • 6 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt.
  • 7 Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
  • 8 School of Health and Biomedical Sciences, RMIT University, Melbourne 3083, Australia.
  • 9 The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo 11651, Egypt.
  • 10 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza 12566, Egypt.
  • 11 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia St., Alexandria 21648, Egypt; Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo 12622, Egypt.
PMID: 39244971 DOI: 10.1016/j.bioorg.2024.107778
Abstract

In the current medical era, human health is confronted with various challenges, with Cancer being a prominent concern. Therefore, enhancing the therapeutic arsenal for Cancer with a constant influx of novel molecules that selectively target tumor cells while displaying minimal toxicity toward normal cells is imperative. This study delves into the antiproliferative and EGFR kinase inhibitory activities of newly reported spirooxindole-pyrazolo[3,4-b]pyridine derivatives 8a-h and 10a-h. The inhibitory effects on the growth of human Cancer cell lines A-549 (lung carcinoma), Panc-1 (pancreatic carcinoma), and A-431 (skin epidermoid carcinoma) were evaluated, and the SAR has been clarified through analysis. With IC50 values in the single-digit micromolar range, compounds 8b, 8d, 10a-b, and 10d were shown to be the most effective antiproliferative candidates against the studied Cancer cell lines. They also exerted negligible cytotoxicity (with selectivity scores between 8.63 and 30.02) against the human lung MRC5 cell line. Additionally, we investigated the potential inhibitory action of compounds 8b, 8d, 10a-b, and 10d on EGFR and VEGFR-2. 10a was this investigation's most effective EGFR inhibitor, with an IC50 value of 0.54 μM. Ultimately, the molecular docking analysis of congener 10a highlighted its effective suppression of EGFR by examining its binding mode and docking score compared to Erlotinib. These findings underscore the potential of spirooxindole-pyrazolo[3,4-b]pyridine derivatives as promising Anticancer agents targeting EGFR kinase.

Keywords

Biological evaluations; Isatin; Kinase inhibitor; Molecular Docking; Pancreatic cancer; Skin Cancer; Synthesis.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-168064
    EGFR Inhibitor