2. Academic Validation
  3. Cancer Cells Show Higher Sensitivity to Melatonin-Tamoxifen Drug Conjugates than to Combination of Melatonin and Tamoxifen

Cancer Cells Show Higher Sensitivity to Melatonin-Tamoxifen Drug Conjugates than to Combination of Melatonin and Tamoxifen

  • ACS Omega. 2024 Nov 18;9(48):47857-47871. doi: 10.1021/acsomega.4c08881.
Mohamed Akmal Marzouk 1,  Sara Greco 2,  Florence Gbahou 3,  Jenni Küblbeck 4 5,  Nedjma Labani 3,  Ralf Jockers 3,  Ulrike Holzgrabe 1,  Lisa Wiesmüller 2,  Darius P Zlotos 6
Affiliations

Affiliations

  • 1 Institute of Pharmacy and Food Chemistry, University of Würzburg, Würzburg 97074, Germany.
  • 2 Department of Obstetrics and Gynecology, Ulm University, Prittwitzstrasse 43, Ulm 89075, Germany.
  • 3 Université Paris Cité, Institut Cochin, INSERM, CNRS, Paris 75014, France.
  • 4 A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70210, Finland.
  • 5 School of Pharmacy, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70210, Finland.
  • 6 Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, The German University in Cairo, New Cairo City, Cairo 11835, Egypt.
PMID: 39651096 DOI: 10.1021/acsomega.4c08881
Abstract

Drug conjugates of tamoxifen and melatonin linked through the amide side chain of melatonin (4a,4b) were reported as promising agents for future treatment of breast Cancer, possibly reversing the adverse effects of tamoxifen. Here, we report the synthesis and pharmacological evaluation of a novel series of Anticancer drug conjugates linking melatonin with tamoxifen through polymethylene spacers through the ether oxygen of melatonin (16a-c, 19a-c, 21) and compare them to the previously reported amide-linked analogues 4a and 4b. All hybrid ligands are antagonists of Estrogen Receptor alpha and agonists of the melatonin MT1 receptor with variable potencies. Several drug conjugates including the (CH2)4-linked analogues 4a and 16a and the (CH2)6-linked compound 16c showed higher potency to inhibit cell viability than the combination of melatonin and tamoxifen on at least one Cancer cell line including MCF-7, MDA-MB-231, and HT-1080.

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