Emergence of Candida spp. and exploration of natural bioactive molecules for anticandidal therapy –status quo

Abstract

The opportunistic yeast pathogen Candida albicans and the emerging non-albicans Candida spp. cause life-threatening infections in immuno-compromised patients, leading to an increase in mortality rate. At present, the emergence of non-albicans Candida spp. causes serious infections that are difficult to treat the human populations worldwide. The available, synthetic antifungal drugs show high toxicity to host tissues causing adverse effects. Many metabolites of terrestrial and marine plants, microbes, algae, etc., contain a rich source of unexplored novel leads of different types, which are under use to treat various diseases. Such natural drugs are less expensive and have lower toxicity to host tissues. The patent search on identified and potential anticandidal-lead molecules, from various patent databases, has been described in this review. Furthermore, this article consolidates the trends in the development of anticandidal drug discovery worldwide. Most of the investigations on natural, bioactive molecules against candidiasis are in various phases of clinical trials, of which, two drugs Caspofungin acetate and Micafungin sodium were approved by the U.S. FDA. In conclusion, the exploration of drugs from natural resources serves as a better alternative source in anticandidal therapeutics, having great scope for drug discovery in the future.

New pharmacological properties of Medicago sativa and Saponaria officinalis saponin-rich fractions addressed to Candida albicans

“…Meanwhile, the availability of well-established pharmaceutics is greatly reduced due to the rapidly growing number of multidrugresistant strains. The current paradigm in the discovery of novel promising antimicrobial therapeutics postulates their targeting to microbial virulence factors/abilities rather than direct biocidal activity (Bink et al, 2011;Chevalier et al, 2012;Gauwerky et al, 2009;Naicker & Patel, 2013;Rajeshkumar & Sundararaman, 2012). The antifungal potential of tested SFs from plant extracts seems to fulfil these needs.…”

“…Relatively few antimycotic groups have been identified, including polyenes, azoles, echinocandins, allylamines and 5-flucytosine (Kabir & Ahmad, 2013; Pemán et al, 2009;Rajeshkumar & Sundararaman, 2012). Furthermore, the growing resistance of C. albicans and other Candida species to antifungal compounds and the participation of their biofilms in the development of pathological lesions have led to an urgent need to develop alternative therapy.…”

“…A number of factors contribute to the higher resistance of microbial biofilm to environmental stress conditions, including chemotherapeutics and host immune response, thus making biofilm an important aetiological agent of human disease. The reasons for this increased resistance must be sought primarily in the specific structure and unique physiology of this community, and the case of C. albicans biofilm in particular involves various morphological yeast forms and mixed bacterial-fungal biofilms, which are much more difficult to diagnose and treat (Bhattacharyya et al, 2013;Bink et al, 2011;Kabir et al, 2012;Mathé & van Dijck, 2013;Sardi et al, 2013).Relatively few antimycotic groups have been identified, including polyenes, azoles, echinocandins, allylamines and 5-flucytosine (Kabir & Ahmad, 2013; Pemán et al, 2009;Rajeshkumar & Sundararaman, 2012). Furthermore, the growing resistance of C. albicans and other Candida species to antifungal compounds and the participation of their biofilms in the development of pathological lesions have led to an urgent need to develop alternative therapy.…”

“…Scientists and physicians have focused on naturally occurring substances, such as plant-derived compounds (e.g. polyphenols, essential oils, saponins) possessing direct biocidal/biostatic properties against fungi or inhibiting/impairing their virulence factor expression, adhesion and biofilm formation (Abid Ali Khan et al, 2012;Bhattacharyya et al, 2013;Naicker & Patel, 2013;Rajeshkumar & Sundararaman, 2012;Tsuzuki et al, 2007). In this respect, one of the lesser known but promising agents seem to be saponins -surface-active phytochemicals present in most vegetables, beans and herbs.…”

“…The authors explained this phenomenon by an original mechanism of caspofungin action. Caspofungin belongs to echinocandins -cyclic lipopeptides interfering with cell wall biosynthesis by the inhibition of 1,3-b-glucan synthase (Cannon et al, 2009;Rajeshkumar & Sundararaman, 2012;Soustre et al, 2004). Therefore, its influence on the yeast cell wall may lead to a disturbance in the expression of some cellular adhesins.…”