NO-Donor Dihydroartemisinin Derivatives as Multitarget Agents for the Treatment of Cerebral Malaria

被引：20

作者：

Bertinaria, Massimo ^{[1
]}

Orjuela-Sanchez, Pamela ^{[2
]}

Marini, Elisabetta ^{[1
]}

Guglielmo, Stefano ^{[1
]}

Hofer, Anthony ^{[2
]}

Martins, Yuri C. ^{[2
]}

Zanini, Graziela M. ^{[3
]}

Frangos, John A. ^{[2
]}

Gasco, Alberto ^{[1
]}

Fruttero, Roberta ^{[1
]}

Carvalho, Leonardo J. M. ^{[4
]}

机构：

[1] Univ Turin, Dipartimento Sci & Tecnol Farmaco, I-10123 Turin, Italy

[2] La Jolla Bioengn Inst, La Jolla, CA 92037 USA

[3] Fiocruz MS, Inst Nacl Infectol, Lab Parasitol, BR-21040360 Rio De Janeiro, Brazil

[4] Inst Oswaldo Cruz, Lab Pesquisa Malaria, BR-21040900 Rio De Janeiro, Brazil

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 58卷 / 19期

基金：

美国国家卫生研究院;

关键词：

SEVERE FALCIPARUM-MALARIA; NITRIC-OXIDE; CHILDREN; DYSFUNCTION;

D O I：

10.1021/acs.jmedchem.5b01036

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Hybrid products in which the dihydroartemisinin scaffold is combined with NO-donor furoxan and NONOate moieties have been synthesized and studied as potential tools for the treatment of cerebral malaria (CM). The designed products were able to dilate rat aorta strips precontracted with phenylephrine with a NO-dependent mechanism. All hybrid compounds showed preserved antiplasmodial activity in vitro and in vivo against Plasmodium berghei ANKA., comparable to artesunate and artemether. Hybrid 10, selected for additional studies, was capable of increasing survival of mice with late-stage CM from 27.5% to 51.6% compared with artemether. Artemisinin-NO-donor hybrid compounds show promise as potential new drugs for treating cerebral malaria.

引用

收藏

页码：7895 / 7899

页数：5

相关论文

共 21 条

[1] Nitric oxide in Tanzanian children with malaria: Inverse relationship between malaria severity and nitric oxide production nitric oxide synthase type 2 expression [J].

Anstey, NM ;

Weinberg, JB ;

Hassanali, M ;

Mwaikambo, ED ;

Manyenga, D ;

Misukonis, MA ;

Arnelle, DR ;

Hollis, D ;

McDonald, MI ;

Granger, DL .

JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (02) :557-567

[2] Amodiaquine analogues containing NO-donor substructures: Synthesis and their preliminary evaluation as potential tools in the treatment of cerebral malaria [J].

Bertinaria, Massimo ;

Guglielmo, Stefano ;

Rolando, Barbara ;

Giorgis, Marta ;

Aragno, Cristina ;

Fruttero, Roberta ;

Gasco, Alberto ;

Parapini, Silvia ;

Taramelli, Donatella ;

Martins, Yuri C. ;

Carvalho, Leonardo J. M. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (05) :1757-1767

[3] CARDIOVASCULAR ACTIONS OF THE FUROXAN CAS-1609, A NOVEL NITRIC-OXIDE DONOR [J].

BOHN, H ;

BRENDEL, J ;

MARTORANA, PA ;

SCHONAFINGER, K .

BRITISH JOURNAL OF PHARMACOLOGY, 1995, 114 (08) :1605-1612

[4] Cerebral tissue oxygenation impairment during experimental cerebral malaria [J].

Cabrales, Pedro ;

Martins, Yuri C. ;

Ong, Peng Kai ;

Zanini, Graziela M. ;

Frangos, John A. ;

Carvalho, Leonardo J. M. .

VIRULENCE, 2013, 4 (08) :686-697

[5] Nitric Oxide Protection Against Murine Cerebral Malaria Is Associated With Improved Cerebral Microcirculatory Physiology [J].

Cabrales, Pedro ;

Zanini, Graziela M. ;

Meays, Diana ;

Frangos, John A. ;

Carvalho, Leonardo J. M. .

JOURNAL OF INFECTIOUS DISEASES, 2011, 203 (10) :1454-1463

[6] Murine Cerebral Malaria Is Associated with a Vasospasm-Like Microcirculatory Dysfunction, and Survival upon Rescue Treatment Is Markedly Increased by Nimodipine [J].

Cabrales, Pedro ;

Zanini, Graziela M. ;

Meays, Diana ;

Frangos, John A. ;

Carvalho, Leonardo J. M. .

AMERICAN JOURNAL OF PATHOLOGY, 2010, 176 (03) :1306-1315

[7] Persistent neurocognitive impairments associated with severe falciparum malaria in Kenyan children [J].

Carter, JA ;

Mung'ala-Odera, V ;

Neville, BGR ;

Murira, G ;

Mturi, N ;

Musumba, C ;

Newton, CRJC .

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2005, 76 (04) :476-481

[8] Artemether and Artesunate Show the Highest Efficacies in Rescuing Mice with Late-Stage Cerebral Malaria and Rapidly Decrease Leukocyte Accumulation in the Brain [J].

Clemmer, L. ;

Martins, Y. C. ;

Zanini, G. M. ;

Frangos, J. A. ;

Carvalho, L. J. M. .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2011, 55 (04) :1383-1390

[9] Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial [J].

Dondorp, Arjen M. ;

Fanello, Caterina I. ;

Hendriksen, Ilse C. E. ;

Gomes, Ermelinda ;

Seni, Amir ;

Chhaganlal, Kajal D. ;

Bojang, Kalifa ;

Olaosebikan, Rasaq ;

Anunobi, Nkechinyere ;

Maitland, Kathryn ;

Kivaya, Esther ;

Agbenyega, Tsiri ;

Nguah, Samuel Blay ;

Evans, Jennifer ;

Gesase, Samwel ;

Kahabuka, Catherine ;

Mtove, George ;

Nadjm, Behzad ;

Deen, Jacqueline ;

Amumpaire, Juliet Mwanga ;

Nansumba, Margaret ;

Karema, Corine ;

Umulisa, Noella ;

Uwimana, Aline ;

Mokuolu, Olugbenga A. ;

Adedoyin, Olanrewaju T. ;

Johnson, Wahab B. R. ;

Tshefu, Antoinette K. ;

Onyamboko, Marie A. ;

Sakulthaew, Tharisara ;

Ngum, Wirichada Pan ;

Silamut, Kamolrat ;

Stepniewska, Kasia ;

Woodrow, Charles J. ;

Bethell, Delia ;

Wills, Bridget ;

Oneko, Martina ;

Peto, Tim E. ;

von Seidlein, Lorenz ;

Day, Nicholas P. J. ;

White, Nicholas J. .

LANCET, 2010, 376 (9753) :1647-1657

[10] Low nitric oxide bioavailability contributes to the genesis of experimental cerebral malaria [J].

Gramaglia, Irene ;

Sobolewski, Peter ;

Meays, Diana ;

Contreras, Ramiro ;

Nolan, John P. ;

Frangos, John A. ;

Intaglietta, Marcos ;

van der Heyde, Henri C. .

NATURE MEDICINE, 2006, 12 (12) :1417-1422