The aims of this investigation were to isolate active ingredients from the roots/rhizomes of Cyperus articulatus used as herbal medicine in Cameroon for the treatment of human onchocerciasis and to assess the efficacy of the metabolites on the Onchocerca worm. The antifilarial activity was evaluated in vitro on microfilariae (Mfs) and adult worms of the bovine derived Onchocerca ochengi, a close relative of Onchocerca volvulus. Cytotoxicity was assessed in vitro on monkey kidney epithelial cells. The structures of the active compounds were determined using spectroscopic methods and their drug-likeness evaluated using Lipinski parameters. Two secondary metabolites, AMJ1 [containing mustakone (1) as the major component] and linoleic acid or (9Z,12Z)-octadeca-9,12-dienoic acid (2) were isolated. Both compounds were found to kill both the microfilariae and adult worms of O. ochengi in a dose dependent manner. The IC50s for AMJ1 were 15.7 µg/mL for Mfs, 17.4 µg/mL for adult males and 21.9 µg/mL for adult female worms while for linoleic acid the values were, 15.7 µg/mL for Mfs, 31.0 µg/mL for adult males and 44.2 µg/mL for adult females. The present report provides the first ever evidence of the anti-Onchocerca efficacy of AMJ1 and linoleic acid. Thus, these secondary metabolites may provide a lead for design and development of new antifilarial agents.Electronic supplementary materialThe online version of this article (doi:10.1007/s13659-014-0023-5) contains supplementary material, which is available to authorized users.

Abstract Our previous work was focused on the fundamental physical and chemical concepts behind “drug-likeness” and “natural product (NP)-likeness”. Herein, we discuss further details on the concepts of “drug-likeness”, “lead-likeness” and “NP-likeness”. The discussion will first focus on NPs as drugs, then a discussion of previous studies in which the complexities of the scaffolds and chemical space of naturally occurring compounds have been compared with synthetic, semisynthetic compounds and the Food and Drug Administration-approved drugs. This is followed by guiding principles for designing “drug-like” natural product libraries for lead compound discovery purposes. In addition, we present a tool for measuring “NP-likeness” of compounds and a brief presentation of machine-learning approaches. A binary quantitative structure–activity relationship for classifying drugs from nondrugs and natural compounds from nonnatural ones is also described. While the studies add to the plethora of recently published works on the “drug-likeness” of NPs, it no doubt increases our understanding of the physicochemical properties that make NPs fall within the ranges associated with “drug-like” molecules.

Two novel Schiff bases, 3-[1-(2-(phthalazin-1-yl)hydrazono)ethyl)-1,3-oxazinane (PHEO) and 2-[(2-(phthalazin-1-yl)hydrazono)methyl]phenol (PHMP), derived from hydralazine hydrochloride, an effective drug against hypertension, were synthesized and characterized by spectroscopic methods, Infrared (IR), Proton Nuclear Magnetic Resonance (1 H NMR) and Carbon-13 Nuclear Magnetic Resonance (13 C NMR). PHEO showed low antimicrobial activity against one bacterial strain with MIC value of 250 µg/ml while PHMP showed interesting activity against 4 bacterial strains with MIC of 31.25-250 µg/ml compared to the standard drug, amoxicillin. PHEO and PHMP showed higher reducing activity on ferric ions compared to Vitamin C. On lipid peroxidation, PHEO showed higher inhibition while PHMP showed lower inhibition compared to Vitamin C. Both compounds presented lower stimulating effect and lower catalase activity compared to the standard Vitamin C. PHEO and PHMP showed less than 80% inhibition in the preliminary antiplasmodial assay and so were not considered for the dose-response studies.

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