Anti-proliferate Activity and 5α-reductase Inhibitors of Chiral Macrocyclic (Nα-di-nicotinoyl)[L-phenylalaninyl-L-leucinyl]Pentapeptide Candidates Against LNCaP and PC-3 Prostate Cancer Cell Lines

Abstract

A series of macrocyclic derivatives <strong>2-6</strong> were prepared using N^α-dinicotinoyl-bis[L-phenylalaninyl-L-leucyl]hydrazide <strong>1</strong> and cyclo pentapeptide hydrazide <strong>2 </strong>as starting materials. The hydrazide <strong>1 </strong>was cyclized with diaminoalkanes to macrocyclic hezaazahexaamide derivatives <strong>3a-c</strong>, respectively. Finally, compound<strong>2</strong> was condensed with 3,5-diacetylpyridine gave the corresponding macrocyclic Schiff base <strong>4</strong>. Finally, condensation of <strong>2</strong> with substituted aromatic or heterocyclic aldehyde derivatives gave the corresponding Schiff base derivatives <strong>5a-f</strong> and <strong>6a-c</strong>, respectively. The synthesized compounds were screened as 5α-reductase inhibitors and anti-proliferative activity against prostate cancer cell lines.