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  3. Novel cilengitide-based cyclic RGD peptides as αvβ3 integrin inhibitors

Novel cilengitide-based cyclic RGD peptides as αvβ3 integrin inhibitors

  • Bioorg Med Chem Lett. 2020 Apr 15;30(8):127039. doi: 10.1016/j.bmcl.2020.127039.
Chhuttan L Meena 1,  Dharmendra Singh 1,  Michael Weinmüller 2,  Florian Reichart 2,  Abha Dangi 3,  Udaya Kiran Marelli 3,  Stefan Zahler 4,  Gangadhar J Sanjayan 5
Affiliations

Affiliations

  • 1 Division of Organic Chemistry CSIR-National Chemical Laboratory (NCL), Dr. Homi Bhabha Road, Pune 411008, India.
  • 2 Institute for Advanced Study, Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
  • 3 Central NMR Facility, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, 411008 Pune, India.
  • 4 Pharmaceutical Biology, Center for Drug Research, Ludwig-Maximilians-Universität, Butenandtstr. 5-13, 81377 Munich, Germany.
  • 5 Division of Organic Chemistry CSIR-National Chemical Laboratory (NCL), Dr. Homi Bhabha Road, Pune 411008, India. Electronic address: gj.sanjayan@ncl.res.in.
PMID: 32094009 DOI: 10.1016/j.bmcl.2020.127039
Abstract

In this letter, we report a series of five new RGD-containing cyclic Peptides as potent inhibitors to αvβ3 Integrin protein. We have incorporated various unnatural lipophilic Amino acids into the cyclic RGD framework of cilengitide, which is selective for αvβ3 Integrin. All the newly synthesized cyclic Peptides were evaluated in vitrosolid phase binding assay and investigated for their bindingbehaviourtowards Integrin subtypes. All the cyclic Peptides were synthesized in excellent yield following solution-phase coupling strategy. The cyclic RGD Peptides 1a-e exhibited IC50 of 9.9, 5.5, 72, 11 and 3.3 nM, respectively, towardsαvβ3 Integrin protein. This finding offers further opportunities for the introduction unusual Amino acids into the cyclic peptide framework of cilengitide.

Keywords

Anticancer drugs; Cilengitide; Integrins; RGD cyclicpeptides.

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