Potent dual inhibitors of Plasmodium falciparum M1 and M17 aminopeptidases through optimization of S1 pocket interactions

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Potent dual inhibitors of Plasmodium falciparum M1 and M17 aminopeptidases through optimization of S1 pocket interactions

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作者：Nyssa Drinkwater^a ; ^b ; ¹ ; Natalie B. Vinh^c ; ¹ ; Shailesh N. Mistry^c ; ¹ ; ³ ; Rebecca S. Bamert^a ; ^b ; Chiara Ruggeri^g ; John P. Holleran^f ; Sasdekumar Loganathan^f ; Alessandro Paiardini^e ; Susan A. Charman^d ; Andrew K. Powell^d ; Vicky M. Avery^f ; Sheena McGowan^a ; ^b ; ² ; ^{Sheena.McGowan@monash.edu" class="auth_mail" title="E-mail the corresponding author} ; Peter J. Scammells^c ; ² ; ^{Peter.Scammells@monash.edu" class="auth_mail" title="E-mail the corresponding author}
关键词：Plasmodium falciparum ; Malaria ; Aminopeptidase inhibitors ; Hydroxamic acid ; Zinc-binding group
刊名：European Journal of Medicinal Chemistry
出版年：2016
出版时间：3 March 2016
年：2016
卷：110
期：Complete
页码：43-64
全文大小：1595 K

文摘

class="label">•: Dual inhibition of PfA-M1 and PfA-M17 is proposed as a novel antimalarial strategy.
class="label">•: Compound series containing hydroxamic acid zinc binding group optimized by SBDD.
class="label">•: Compounds elaborated into S1 pockets of PfA-M1 and PfA-M17.
class="label">•: Optimized compounds possess superior PfA-M1 and PfA-M17 inhibitory activity.
class="label">•: The potent, dual inhibitors inhibit multi-drug resistant Pf growth in culture.

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