Synthesis of chiral 3,5-bis(l-phenylalaninyl-l-leucinyl)pyridine Schiff base and their macrocyclic carboxaimide derivatives using 3,5-bis(l-phenylalaninyl)-pyridine methyl ester

Abstract

A series of linear tetrapeptides 2-7 and cyclooctapeptedopyridine derivatives 8 and 9, were synthesized using N α -dinicotinoyl-bis[(l-phenylalaninyl-l-leucyl) hydrazide] 2 as starting material. Acid hydrazide 2 was reacted with aromatic or heterocyclic aldehydes to give Schiff base derivatives 3 and 4, respectively. Additionally, compound 2 was reacted with dicarboxylic acid anhydrides ortetracarboxylic diacid anhydrides to give the corresponding linear diimide carboxamides 5-7, and octapeptide tetraimides 8 and 9, respectively. The synthesized products were elucidated by using spectroscopic evidences and they were evaluated for their antibacterial activity by using streptomycin as reference antibiotic drug.

Chiral Pyridine-3,5-bis- (L-phenylalaninyl-L-leucinyl) Schiff Base Peptides as Potential Anticancer Agents: Design, Synthesis, and Molecular Docking Studies Targeting Lactate Dehydrogenase-A

“…In the present work, some of the prepared tetrapeptide derivatives 3-6 were obtained from N α -dipicolinoyl-bis[(l-phenylalanyl-l-leucine)hydrazide] 2, which was obtained from corresponding ester 1 [39]. Reaction of hydrazide 2 with cycloalkanone derivatives in refluxing glacial acetic acid afforded the corresponding N α -dipicolinoyl-bis[(l-phenylalanyl-l-leucine)-N'-cycloalkylidenehydrazide] 3a-d. Condensation of 2 with active carbonyl derivatives, namely, acetylpyridine or substituted acetophenone derivatives in refluxing acetic acid, gave the corresponding N α -dipicolinoyl-bis[(l-phenylalanyl-l-leucine)-N'-(1-(pyridyl)ethylidene)benzohydrazide] 4a-c and N α -dipicolinoyl-bis-[(l-phenylalanyl-l-leucine)-N'-(1-(substituted phenyl) ethylidene)benzohydrazide] 5a-e, respectively.…”

“…Analytical thin layer chromatography (TLC) was performed on silica gel aluminum sheets, 60 F 254 (E. Merck). Compound 2 was prepared according to our previous reported procedure [39]. N 3 ,N 5 -Bis{1-[(1-(2-cyclooctylidenehydrazinyl)-4-methyl-1-oxopentan-2-yl) N α -dinicotinoyl-bis[L-phenylalaninyl-L-leucyl] Schiff bases 4a-c, 5a-e, and 6a,b.…”

Synthesis and Characterization of Macrocyclic Chiral Tröger’s Base Phenhomazine Candidates as Anticancer Agent

“…Although Tröger base and its analogues have attracted interest of many researcher groups due to their fascinating structures and properties ( Yuan, et al, 2011 ), however, attention has been inadequately focused on these compounds from the biological point of view ( Bailly, et al, 2000 ; Baldeyrou, et al, 2002 ; Manda, et al, 2014 ; Yang, et al, 2015 ). In addition, some of macrocyclic hetero-nitrogen derivatives have been synthesized ( Abu-Ghalia, et al, 2012 ; Amr, et al, 2019 ; Naglah, et al, 2020 ) and have shown promising biological activity, i.e. analgesic and anticonvulsant ( Amr, 2005 ), antimicrobial ( Amr, et al, 2006 ; Azab, et al, 2016 ), anti-proliferative, 5α-reductase inhibiting ( Alanazi, et al, 2020 ), pharmacological ( Al Thagfan, et al, 2018 ), anticancer ( Amr et al, 2018 ), as well as biological activities ( Khayyat and Amr, 2014 ).…”