title: Antiprotozoal, anticancer and antimicrobial activities of dihydroartemisinin acetal dimers and monomers.
abstract: Nine dihydroartemisinin acetal dimers (6-14) with diversely functionalized linker units were synthesized and tested for in vitro antiprotozoal, anticancer and antimicrobial activity. Compounds 6, 7 and 11 [IC(50): 3.0-6.7 nM (D6) and 4.2-5.9 nM (W2)] were appreciably more active than artemisinin (1) [IC(50): 32.9 nM (D6) and 42.5 nM (W2)] against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of the malaria parasite, Plasmodium falciparum. Compounds 10, 13 and 14 displayed enhanced anticancer activity in a number of cell lines compared to the control drug, doxorubicin. The antifungal activity of 7 and 12 against Cryptococcus neoformans (IC(50): 0.16 and 0.55 microM, respectively) was also higher compared to the control drug, amphotericin B. The antileishmanial and antibacterial activities were marginal. A number of dihydroartemisinin acetal monomers (15-17) and a trimer (18) were isolated as byproducts from the dimer synthesis and were also tested for biological activity.
authors.affiliation: National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA. dslade@olemiss.edu
authors.forename: Desmond
authors.initials: D
authors.lastname: Slade
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Galal
authors.forename: Waseem
authors.initials: W
authors.lastname: Gul
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Radwan
authors.forename: Safwat A
authors.initials: SA
authors.lastname: Ahmed
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Jacob
authors.forename: Samir A
authors.initials: SA
authors.lastname: Ross
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Elsohly
mesh_terms: D000080:Acetals / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D037621:Artemisinins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003455:Cryptococcus neoformans / Q000187:drug effects; D019281:Dimerization; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D010963:Plasmodium falciparum / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000080:Acetals; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D000981:Antiprotozoal Agents; D037621:Artemisinins