The nature is an inexhaustible source of secondary metabolites, many of which get to be true pharmacological tools that can either have a therapeutic utility or help to understand the several metabolic processes. Generally secondary metabolites are substances non essential for the organism and its production can be conditioned by external factors. The biological properties of these compounds are very different: antitumoral, antioxidant, cytostatic, immunomodulatory, antifungal, antibiotic, insecticidal or anti-inflammatory. In fact, these metabolites have been a main source of resources for the pharmaceutical industry in the last century. They are mainly isolated from superior plants, marine organisms, microscopic fungi and bacteria. The variety of structures obtained and the different therapeutic activities shown for the natural products make that the isolation, identification, synthesis and bioassays of new natural compounds continue being a field of enormous interest. Development of spectroscopic techniques in the last decades allows in most of the cases the elucidation of the complete structure.
In this way, our group of research has been working for years in the isolation, elucidation, chemical transformation and syntheses of diverse compounds of natural origin, coming from terrestrial fungal extracts with insecticidal, antifungal, bactericidal, antioxidant and cytotoxic activities. In the present work, continuing with the methodology of the Centro de Ecología Química Agrícola (CEQA) in the Universitat Politècnica de València, has been studied the organic extracts of different microfungi: Aspergillus ochraceus Wilhelm, Penicillium cluniae Quintanilla and Penicillium coalescens Quintanilla like sources of biometabolites with possible pharmacological or insecticidal applications.
From the extract of the organic broth of A. ochraceus, that showed cytostatic activity, four compounds have been isolated: stephacidin A, circumdatin E, circumdatin H and flavacol, being the first one the cytostatic compound. All these molecules have been found previously in this same species, with exception of circumdatin H which has been depicted in the nature for the first time.
From the organic broth of P. cluniae, that showed cytostatic and insecticidal activity against Oncopeltus fasciatus Dallas, have been isolated thirteen compounds: one of them is brefeldin A, five of them belong to the diketopiperazines’ group: Ciclo-(L-Pro-L-Tyr), Ciclo-(L-Pro-L-Val), Ciclo-(L-Pro-L-Ileu), Ciclo-(L-Pro-L-Leu) and Ciclo-(L-Pro-L-Phe) and the other seven compounds belong to the paraherquamide family: VM55596, PHQ-I, PHQ-H, PHQ-A, PHQ-B, PHQ-E and VM55597. Although these molecules have been described in other fungal species, with the exception of the new compounds PHQ-H and PHQ-I, none of them have been previously isolated in P. cluniae. Structure-activity relationships studies have been carried out, being necessary to emphasize the insecticidal activity of PHQ-E with a DL50 0,089 mg/nymph (0,086, 0.092).
Finally, two different strains from P. coalescens with strong insecticidal activity against the hemipteran O. fasciatus and the dipteran Ceratitis capitata Wiedmann in the preliminary screening have been studied, being botryodiplodin, a well-known mycotoxin, the insecticidal agent. This insecticidal property for botryodiplodin has not been described in bibliography until the moment. In addition six new structural analogs of botryodiplodin have been isolated: botryodioxinenone, ethoxyphenyl-botryodiplodin, botryodiplodinenone, botryodioxindinenone, 2-epi-botryodiplodinenone and the dimer of botryodiplodin.