Indolizidine, antiinfective and antiparasitic compounds from Prosopis glandulosa var. glandulosa.

Plants of the genus Prosopis are trees or shrubs distributed in arid and semiarid tropical and subtropical regions. P. glandulosa Torrey var. glandulosa (Leguminosae), a medium-sized tree, is one of the two varieties of honey mesquite available in North America.1,2 Generally, mesquite is a popular adjuvant for preparing smoked cuisine in the southern part of the U.S. Many tribes of the southwestern United States and Mexico have long utilized the medicinal values of this plant, including treatment of eye infections, open wounds, dermatological ailments and stomach problems.3,4 Decoctions of leaves and pods are generally used to make eye washes to treat pink eye.5 An ethanolic extract of P. glandulosa from Pakistan yielded triterpenes, flavonoids, glycosides and the indolizidine alkaloid juliprosopine.6–10 Among the indolizidines reported from Prosopis species to date,6–11 the stereochemistry of juliprosine and juliprosopine were established by chemical synthesis.12 The piperidinyl indolizidines, such as juliprosopine, and their analogs exhibited in vitro antibmicrobial, antidermatophytic, pesticidal, and amebicidal activities.11,13–20 In addition, their toxicity,20–22 DNA binding activity23, inhibitory effects on β-glucosidase enzymes23 and plant growth inhibitory activities were also reported.10,24 This paper describes the isolation of the new potent antifungal and antimalarial dihydroindolizinium chloride prosopilosidine (1) from honey mesquite, together with three new analogs prosopilosine (2), isoprosopilosine (3) and isoprosopilosidine (4), and the known juliprosopine (5).25,26 P. glandulosa Torrey var. glandulosa, has not previously been subjected to chemical or biological investigations. Prosopilosidine (1) possesses the pharmacophore 2,3-dihydro-1H-indolizinium, a quaternary salt substituted with two units of 10-(5R-hydroxy-6R-methylpiperidin-2R-yl)decyl at C-6‴ and C-8‴ positions. In this paper, we report the isolation, structure elucidation, and in vitro and in vivo antiinfective, antimalarial and cytoxic evaluation of these compounds.