Planta Medica International Open 2017; 4(S 01): S1-S202
DOI: 10.1055/s-0037-1608304
Lecture Session – Phytopharmacology/Extract Pharmacology I
Georg Thieme Verlag KG Stuttgart · New York

Drug discovery approaches against Madurella mycetomatis – one of the most neglected tropical diseases (NTDs)

S Khalid
1   1 Faculty of Pharmacy, University of Science and Technology, P. O. Box 477 Omdurman, Sudan. 2 Faculty of Pharmacy, University of Khartoum, P. O. Box 1996, Khartoum, Sudan, Khartoum, Sudan
› Author Affiliations
Further Information

Publication History

Publication Date:
24 October 2017 (online)

 

Madurella mycetomatis is a severe eumycotic infection caused by a stubborn fungus. It is characterized with uniques clinical manifestation involving the skin and subcutaneous tissue. The infection can keep spreading until it ereaches the bones and distant sites through the blood and lymph which eventually leads to destruction, deformity and loss of function [1]. Due to the increadsing burden of M. mycetomatis and the multiple gaps in our knowledge about this disease, the 69th World Health Assembly (WHA) adopted an important resolution in May 2016 adding mycetoma to the list of NTDs and calling on al actors to join forces to control the public-health impact of this disfiguring and life threatening disease.

Prolonged treatment of M. mycetomatis with almost all currently available antifungal agents proved to be of disappointing clinical efficacy which usually associated with severe side effects and frequently results in amputation [2]. This warranted us to collect a dozen of clinical strains M. mycetomati from Sudanese patients followed by culturing and profiling of their susceptibility against eight known antifungal agents representing five azoles (ketoconazole, itraconazole, voriconazole, posaconazole, fluconazole) besides an allylamine (terbinafine), a polyene macrolide (amphotericin B), and a lipopeptide echinocandin (caspofungin).

The validity of our inhouse established in vitro screening method [3], was further consolidated by subjecting a series of plant secondary metabolites including, terpenoids, polyphenols and alkaloids. Among the later class, the protoberberine (e.g. berberine), benzophenanthridine (e.g sanguinarine), and β-carboline (e.g. harmine) alkaloids exhibited appreciable activities. Sanguinarine exhibited a remarkable in vitro activity with MIC50 and MIC90 of 1 and 4, respectively.

[1] Fahal AH, 1992, British Journal Surgery, 79, 1138 – 1141.

[2] Abbott PH, Transactions of the Royal Society of Tropical Medicine and Hygiene. 1956; 50: 11 – 24.

[3] Khalid SA, 2014, ResNet NPND workshop, Nov. 25 – 28th, 2014, Rio de Janeiro, Brazil.