Synthesis and Antileishmanial Activity of Some Functionalized Peptoids

Abstract

We describe the microwave-assisted synthesis of thirteen functionalized peptoids and evaluate their in vitro antileishmanial activity against forms of Leishmania (Leishmania) amazonensis promastigotes. Synthesis via the Ugi four-component reaction (Ugi 4CR) reaction furnished the compounds of interest in 55-80% yield; reactions were conducted in a microwave reactor and lasted only 10 min. We then screened the antileishmanial activity of the synthesized compounds in vitro. To determine the IC 50 (inhibitory concentration necessary to inhibit the growth of 50% of parasites) values, we selected the compounds that inhibited L. (L.) amazonensis growth by more than 50%. The seven selected compounds displayed IC 50 values ranging from 2.6 to 72 μM after incubation for 48 h. Three peptoids gave IC 50 values between 2.6 and 7.9 μM and can be considered as bioreactive molecules (hit criteria).

Sequence-controlled and sequence-defined polypeptoidsviathe Ugi reaction: synthesis and sequence-driven properties

“…50 Inspired by the above challenges, the Ugi reaction is considered to be a good method. [51][52][53][54][55] The Ugi reaction was first reported by the German chemist Ivar Karl Ugi in 1959. 56 In the development of a multicomponent reaction, this reaction was only used for crosslinking sodium alginate.…”

Antiparasitic effect of peptoids againstCryptosporidium parvum

“…Unlike traditional antimicrobials, peptoids are less prone to the rapid development of resistance, making them a promising avenue for novel therapeutic development [8,9]. To date few studies have investigated the use of peptoids in parasites, all in Leishmania species [10][11][12]. In this study we investigate the antiparasitic effect of synthetic peptoids against C. parvum.…”

“…The library of 14 peptoids were diluted to five concentrations (5,10,20, 40 and 80 µg/mL) in RPMI 1640, no phenol red media (ThermoFisher Scientific #11835030) plus 3% horse serum (ThermoFisher Scientific #26050070). C. parvum sporozoites were released from the oocysts by pre-treating the oocysts with 1:4 dilution of household bleach for 10 minutes on ice, followed by incubating in 0.75% sodium taurocholate (Sapphire Bioscience #16214) for 45 minutes at 37°C.…”

Membrane‐acting biomimetic peptoids against visceral leishmaniasis

“…As a result of this structural difference, peptoids often exhibit decreased susceptibility to proteolytic degradation and better stability, functional versatility, and bioavailability than their peptide counterparts [ 16 , 19 ]. Peptoids have shown activity against various pathogens, including viruses, bacteria, fungus, and parasites [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. However, most of the parasite studies have been carried out against either L. amazonensis promastigotes [ 25 , 28 ] or L. mexicana axenic amastigotes [ 29 ].…”

“…Peptoids have shown activity against various pathogens, including viruses, bacteria, fungus, and parasites [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. However, most of the parasite studies have been carried out against either L. amazonensis promastigotes [ 25 , 28 ] or L. mexicana axenic amastigotes [ 29 ]. To the best of our knowledge, the present study is the first report to successfully assess the effect of peptoids against L. donovani in both forms (intracellular amastigotes and promastigotes).…”