PubMed · 15206458
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J D Connolly, R A Hill, B T Ngadjui. 1994. Triterpenoids.. https://doi.org/10.1039/np9941100091
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Parnafungins A-D (1-4) are fungal natural products that inhibit eukaryotic poly(A)-polymerase and were first discovered by Merck & Co., Inc., through a Candida albicans Fitness Test (CaFT) screening program. The biological activity of parnafungins is a result of the unique fused hexacyclic structure highlighted by a 5-isoxazolidinone (5ILD) N-heterocycle. In this work, we characterize the complete biosynthetic pathway of parnafungins through heterologous reconstitution and enzymatic assays. Nearly half of the 26-gene biosynthetic gene cluster of parnafungin is responsible for the production of a known polyketide natural product, blennolide C. Starting from the blennolide C fragment, a three-enzyme cascade involving CoA-ligase ParJ, P450 ParO, and DUF829 ParD catalyzes the formal biaryl cross-coupling between blennolide C and anthranilate. Subsequent oxidative cyclization generates a phenanthridine product that is then reduced by atypical short-chain reductase ParT. N-Hydroxylation by flavin-dependent monooxygenase ParB and subsequent lactonization catalyzed by a homologue of dienenolactone hydrolase ParF form the 5ILD ring and complete the biosynthesis of 1 and 2. Methylation of 1 forms parnafungin C (3), and lastly epoxidation forms parnafungin D (4). Together, our work revealed the chemical logic and enzymology in extending the biosynthetic pathway of a well-characterized natural product, blennolide C, to introduce considerable additional structural diversity that affords parnafungins with unique biological activity.
This work presents a study QSAR among the MAO A inhibitory activity (IMAO A) of a xanthones series correlated with descriptors like the E-state index (S(i)), molecular connectivity (chi) and shape (k) descriptors. The xanthones group (9-H-xanton-9-onas) are of natural or synthetic origin, they present eight positions for the substitution and their MAO A inhibitory activity is reported in the work from Gnerre et al. The descriptors included in the adjusted model were selected to describe the molecular structure of the compounds. The model was selected using the leave-one-out method, the cross-validation statistics indicate a model useful for prediction: r(2)=0.847 and s=8.069, calculated by multiple linear regression.
1,5-Anhydroxylitol, a compound never found previously in the vegetal kingdom was obtained from Olea europaea leaves in approximately 0.5-1% yield.