Synthesis of new betulinic acid/betulin-derived dimers and hybrids with potent antimalarial and antiviral activities. Issue 1 (1st January 2019)

• Record Type: Journal Article
• Authors: Karagöz, Aysun Çapcı; Leidenberger, Maria; Hahn, Friedrich; Hampel, Frank; Friedrich, Oliver; Marschall, Manfred; Kappes, Barbara; Tsogoeva, Svetlana B.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 27:Issue 1(2019)
• Page Start: 110
• Page End: 115
• Publication Date: 2019-01-01
• Subjects: DHA dihydroartemisinin -- DMAP 4-(dimethylamino)-pyridine -- DCC N, N'-dicyclohexylcarbodiimide -- EC50 half maximal effective concentration -- EtOAc ethylacetate -- HCMV human cytomegalovirus -- TMSOTf trimethylsilyl triflate -- TLC thin layer chromatography -- P. falciparum Plasmodium falciparum -- UV ultraviolet; Betulin -- Betulinic acid -- Artesunic acid -- Ferrocene -- Natural product hybrid -- Antimalarial activity -- Antiviral activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.11.018
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Severe malaria and viral infections cause life-threatening diseases in millions of people worldwide every year. In search for effective bioactive hybrid molecules, which may possess improved properties compared to their parent compounds, a series of betulinic acid/betulin based dimer and hybrid compounds carrying ferrocene and/or artesunic acid moieties, was designed and, synthesized de novo . Furthermore, they were analyzed in vitro against malaria parasites ( growth inhibition of 3D7-strain P. falciparum-infected erythrocytes) and human cytomegalovirus (HCMV). From this series of hybrids/dimers, the betulinic acid/betulin and artesunic acid hybrids11 and12 showed the most potent activities against P. falciparum and HCMV. On the strength of results, additive and/or synergistic effects between the natural or semisynthetic products, such as betulinic acid-/betulin- and artesunic acid-derived compounds, are suggested on the basis of putatively complex modes of antimicrobial action. This advantage may be taken into account in future drug development.