2. Academic Validation
  3. Design, molecular modelling and synthesis of novel benzothiazole derivatives as BCL-2 inhibitors

Design, molecular modelling and synthesis of novel benzothiazole derivatives as BCL-2 inhibitors

  • Sci Rep. 2023 Sep 20;13(1):15554. doi: 10.1038/s41598-023-41783-1.
Hoda S Ismail 1,  Amira Khalil 2,  Rabah A Taha 1,  Deena S Lasheen 1,  Dalal A Abou El Ella 3
Affiliations

Affiliations

  • 1 Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
  • 2 Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt (BUE), El-Sherouk City, Cairo, 11837, Egypt. [email protected].
  • 3 Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. [email protected].
PMID: 37730790 DOI: 10.1038/s41598-023-41783-1
Abstract

Apoptosis plays a crucial role in Cancer pathogenesis and drug resistance. Bcl-2 Family of enzymes is considered as one of the key enzymes which is involved in Apoptosis. When there is disruption in the balance between anti-apoptotic and pro-apoptotic members of the Bcl-2 Family apoptosis is dysregulated in the affected cells. Herein, 33 novel benzothiazole-based molecules 7a-i, 8a-f, 9a-b, 12a-e, 13a-d, 14a,b, and 17a-j were designed, synthesized and tested for their Bcl-2 inhibitory activity. Scaffold hopping strategy was applied in designing of the target compounds. Compounds 13c and 13d showed the highest activity with IC50 values equal to 0.471 and 0.363 µM, respectively. Molecular docking studies of the synthesized compounds showed comparable binding interactions with the lead compound. Structure activity relationship study was performed to show the effects of structural modifications on the inhibitory activities on Bcl-2.

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