TY - JOUR

T1 - Conjugates of an antimicrobial peptide and usnic acid derivatives targeting resistant cancer cells

AU - O’Flaherty, Siobhán

AU - Krier, Ysaline

AU - Varbanov, Mihayl

AU - Лузина, Ольга Анатольевна

AU - Покровский, Михаил Андреевич

AU - Покровский, Андрей Георгиевич

AU - Dyrkheeva, Nadezhda S.

AU - Zakharenko, Alexandra L.

AU - Лаврик, Ольга Ивановна

AU - Волчо, Константин Петрович

AU - Салахутдинов, Нариман Фаридович

AU - Devocelle, Marc

N1 - Acknowledgments: This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grant Number 12/RC/2275_P2. This research was also co-funded by the Erasmus+ Programme of the European Union. Conjugates of an antimicrobial peptide and usnic acid derivatives targeting resistant cancer cells / Siobhán O'Flaherty, Ysaline Krier, Mihayl Varbanov, Olga A. Luzina, Mikhail A. Pokrovsky, Nadezhda S. Dyrkheeva, Alexandra L. Zakharenko, Andrey G. Pokrovsky, Olga I. Lavrik, Konstantin P. Volcho, Nariman F. Salakhutdinov and Marc Devocelle // Abstracts // Journal of Peptide Science. – 2022. – Vol. 28, No. S3. – DOI 10.1002/psc.3445

PY - 2022/8

Y1 - 2022/8

N2 - Found in all living organisms, antimicrobial peptides (AMPs) contribute to host defence mechanisms. Some amphipathic AMPs have been shown to possess anticancer activity against a broad spectrum of human cancer cells both in vitro and in vivo. However, their drug-like properties remain to be optimised. Conjugation of an AMP to a small-molecule drug can potentially provide improved efficacy, reduced systemic toxicity and improved pharmacokinetics/pharmacodynamics of the components compared with monotherapies. Alternatively, such a conjugate could be utilised as an adjuvant therapy to current cancer treatments. Building on this, a new set of usnic acid derivatives with hydrazinothiazole and benzylidenefuranone pharmacophore moieties have been identified as promising anticancer agents, targeting the human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1). Conjugation of L-K6, a lysine/leucine rich AMP of predetermined anticancer activity, to two highly potent TDP1 inhibitors via hydrazinoacetic acid linkage exhibited pleiotropic effects, ranging from, overall, reduction of the activity from the parent drugs, to their conservation or even enhancement.

AB - Found in all living organisms, antimicrobial peptides (AMPs) contribute to host defence mechanisms. Some amphipathic AMPs have been shown to possess anticancer activity against a broad spectrum of human cancer cells both in vitro and in vivo. However, their drug-like properties remain to be optimised. Conjugation of an AMP to a small-molecule drug can potentially provide improved efficacy, reduced systemic toxicity and improved pharmacokinetics/pharmacodynamics of the components compared with monotherapies. Alternatively, such a conjugate could be utilised as an adjuvant therapy to current cancer treatments. Building on this, a new set of usnic acid derivatives with hydrazinothiazole and benzylidenefuranone pharmacophore moieties have been identified as promising anticancer agents, targeting the human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1). Conjugation of L-K6, a lysine/leucine rich AMP of predetermined anticancer activity, to two highly potent TDP1 inhibitors via hydrazinoacetic acid linkage exhibited pleiotropic effects, ranging from, overall, reduction of the activity from the parent drugs, to their conservation or even enhancement.

UR - https://onlinelibrary.wiley.com/doi/10.1002/psc.3445

UR - https://www.elibrary.ru/item.asp?id=59629254

U2 - 10.1002/psc.3445

DO - 10.1002/psc.3445

M3 - Meeting Abstract

VL - 28

JO - Journal of peptide science

JF - Journal of peptide science

SN - 1075-2617

IS - S3

M1 - P324

T2 - 36th European Peptide Symposium - 12th International Peptide Symposium

Y2 - 28 August 2022 through 2 September 2022

ER -