The Long and Winding Road to Convert an Antimicrobial Compound into an Antimicrobial Drug: An Overview from a Medicinal Chemistry Point of View

ENRIZ, RICARDO D.; SUVIRE, FERNANDO D.; ANDUJAR, SEBASTIAN A.; ALVAREZ, MARIA A.; DOLAB, JUAN G.; VETTORAZZI, MARCELA; ROJAS, SEBASTIAN

CURRENT ORGANIC CHEMISTRY

BENTHAM SCIENCE PUBL LTD

Año: 2017 vol. 21

1385-2728

Fungi have emerged over the past decades as major causes of human infections, especiallyamong immunocompromised hosts. Although it appears that we have a big armamentarium of antifungal drugs in clinicaluse, in fact only a modest number of drugs are available. Unfortunately, all antifungal drugs available for the treatment offungal infections are not fully effective and possess a certain degree of toxicity or some drawbacks in pharmacokineticaspects such as do not possess an adequate solubility. As complement, fungi have developed a rapid resistance againstthem because of their large-scale use. Considering such situation, it is clear an urgent need to develop new and moreeffective antifungal drugs. For such reason in recent years there has been an incredible increase in the number of studieslooking for new compounds with antifungal effects; in particular new structures obtained from natural products. Whilethere have been reported a large number of compounds with antifungal activities (some of them with novel structures),very few have managed to be used therapeutically. In this review article, we have identified and discussed the mainreasons for the poor results that have been obtained so far in order to find new antifungal drugs. Also new strategies whichcould be the way to improve the search for new antifungal agents for therapeutic use are discussed here, remarking itsscope and limitations.