2. Academic Validation
  3. In-vitro and in-silico study to assess anti breast cancer potential of N-tosyl-indole based hydrazones

In-vitro and in-silico study to assess anti breast cancer potential of N-tosyl-indole based hydrazones

  • Sci Rep. 2025 Oct 13;15(1):35733. doi: 10.1038/s41598-025-21326-6.
Uzma Ghaffar 1,  Faizullah Khan 2 3,  Javid Hussain 4,  Suraj N Mali 5,  Ajmal Khan 6 7,  Somdatta Y Chaudhari 8,  Rahul D Jawarkar 9,  Abdullah K Alanazi 10,  Waseem Ul Islam 2,  Mostafa A Ismail 11,  Ahmed Al-Harrasi 12,  Zahid Shafiq 13
Affiliations

Affiliations

  • 1 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan.
  • 2 Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan, KPK, Pakistan.
  • 3 Natural and Medical Sciences Research Centre, University of Nizwa, P.O. Box 33, PC 616, Birkat Al Mauz, Nizwa, Sultanate of Oman.
  • 4 Department of Biological Sciences and Chemistry, University of Nizwa, Nizwa, Oman.
  • 5 Department of Pharmaceutical Chemistry, School of Pharmacy, Dr. D.Y. Patil Deemed to be University, Navi Mumbai, India.
  • 6 Natural and Medical Sciences Research Centre, University of Nizwa, P.O. Box 33, PC 616, Birkat Al Mauz, Nizwa, Sultanate of Oman. ajmalkhan@unizwa.edu.om.
  • 7 Department of Chemical and Biological Engineering, College of Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea. ajmalkhan@unizwa.edu.om.
  • 8 Department of Pharmaceutical Chemistry, Modern College of Pharmacy, Nigdi, Pune, India.
  • 9 Department of Pharmaceutical Chemistry, Dr. Rajendra Gode Institute of Pharmacy, University-Mardi Road, Ghatkheda, Amravati, 444602, Maharashtra, India.
  • 10 Department of Chemistry, College of Science, Taif University, Taif, Saudi Arabia.
  • 11 Department of Chemistry, Faculty of Science, Research Center for Advanced Materials Science (RCAMS), King Khalid University, P.O. Box 960, Abha, 61421, Saudi Arabia.
  • 12 Natural and Medical Sciences Research Centre, University of Nizwa, P.O. Box 33, PC 616, Birkat Al Mauz, Nizwa, Sultanate of Oman. aharrasi@unizwa.edu.om.
  • 13 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan. zahidshafiq@bzu.edu.pk.
PMID: 41083696 DOI: 10.1038/s41598-025-21326-6
Abstract

The main objective of research worldwide is targeting particular genes and proteins vital for the development and viability of Cancer cells. This recent research explores the synthesis and biological evaluation of N-tosyl indole-3-carbaldehyde based hydrazones 5(a-r) as anti-breast Cancer (BC) agents. Two cell lines were employed to evaluate newly synthesized compounds in-vitro; the normal epithelial breast cell line MCF-10 A and the MDA-MB-231 BC cell line. All the synthesized compounds demonstrated significant activity against the BC cell line MDA-MB-231. Compound 5p (IC50 = 12.2 ± 0.4 µM) with a naphthyl group, exhibited promising potential against triple-negative breast Cancer (TNBC) cell line MDA-MB-231. The structures of the compounds 5(a-r) were confirmed by using different characterization techniques such as FT-IR, ¹H NMR, ¹³C NMR, and QTOF HRMS. Molecular docking study demonstrates that compound 5q binds strongly to EGFR (T790M/L858R mutant) with binding energy − 11.533 kcal/mol. However, molecular dynamics show stable interactions with protein 3W2S over 100 ns, supported by favorable RMSD, RMSF and SASA values. These findings hypothesize that compound 5q exerts its Anticancer effect through stable molecular interactions. All synthesized compounds significantly reduced viability in MDA-MB-231 cells compared to normal MCF-10 A cells (p < 0.0001), indicating selective cytotoxicity toward breast Cancer cells.

Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-025-21326-6.

Keywords

Anti-breast cancer; Hydrazone; MD simulation; Molecular docking; N-tosyl-indole.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-179039
    EGFR Inhibitor