2. Academic Validation
  3. Synthesis and biological evaluation of novel penindolone derivatives as potential antiproliferative agents against SCLC in vitro

Synthesis and biological evaluation of novel penindolone derivatives as potential antiproliferative agents against SCLC in vitro

  • Bioorg Med Chem Lett. 2024 Jul 2:110:129877. doi: 10.1016/j.bmcl.2024.129877.
Jiaqi Lin 1,  Yongqing Han 1,  Bohan Li 1,  Wenrui Gai 1,  Zhengjie Wang 1,  Qi Wang 1,  Yueling Teng 1,  Jing Li 2,  Dehai Li 3
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Sanya Oceanographic Institute, Ocean University of China, Qingdao 266003/Sanya 572025, China.
  • 2 Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Sanya Oceanographic Institute, Ocean University of China, Qingdao 266003/Sanya 572025, China; Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China.
  • 3 Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Sanya Oceanographic Institute, Ocean University of China, Qingdao 266003/Sanya 572025, China; Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China. Electronic address: dehaili@ouc.edu.cn.
PMID: 38964518 DOI: 10.1016/j.bmcl.2024.129877
Abstract

Small cell lung Cancer (SCLC) keeps on the leading cause of Cancer mortality world widely, while there is lack of efficient therapeutic drugs especially for the resistant ones. In this work, a compound named penindolone (PND) with new skeleton was found to show weak inhibitory effect (IC50 = 42.5 µM) on H69AR cells (SCLC, adriamycin-resistant) proliferation by screening our in-house compound library. With the aim of improving its low potency, a series of PND derivatives were synthesized and biologically evaluated by the Sulforhodamine B (SRB) assay. Among all tested derivatives, compound 5h possessed higher antiproliferation potency (IC50 = 1.6 µM). Furthermore, preliminary mechanism investigation revealed that 5h was able to induce Apoptosis and arrest the cell cycle at G0/G1 phase. These findings suggest that this novel skeleton has expanded the anti-SCLC compound reservoir and provided a new drug lead.

Keywords

Anti-tumor; H69AR; Penindolone derivatives; Resistance; SCLC.

Figures
Products