Berberine derivatives as antileishmanial drugs

Abstract

Berberine, a quaternary alkaloid, and several of its derivatives were tested for efficacy against Leishmania donovani and Leishmania braziliensis panamensis in golden hamsters. Tetrahydroberberine was less toxic and more potent than berberine against L. donovani but was not as potent as meglumine antimonate (Glucantime), a standard drug for the treatment of leishmaniasis. Only berberine and 8-cyanodihydroberberine showed significant activity (greater than 50% suppression of lesion size) against L. braziliensis panamensis.

(+)-Spectaline, a Piperidine Alkaloid from <i>Senna spectabilis</i> DC. Effective in Reducing the <i>In Vitro</i> Infection of <i>Leishmania major</i>

“…This value seems to be more potent than activity of Amp-B against L.donovani infection on THP-1 which is around 231.02 µg/mL (0.25 µM) [33]. However, this value is less potent compared to berberine (a quaternary alkaloid found in several plant families) with an EC 50 value of 9.08 µg/mL (0.027 µM) [29]. Berberine has been used clinically and applied parenterally for the treatment of CL.…”

“…In a more recent study [28], mixed compounds of major piperidine alkaloids from S. spectabilis flowers extract which consist of (-)-spectaline and (-)-casein have been claimed to be effective against promastigotes of L. major. Through intracellular amastigotes assay model, several pure alkaloids such as berberine [29], liriodenin [30], harmaline [27] and gabunine [31] have been proven for their antileishmanial activity. Table 1 shows the results on the antileishmanial activity of extracts and fractions of S. spectabilis.…”

Antileishmanial Activities of Greek Juniper (Juniperus excelsa M.Bieb.) Against Leishmania major Promastigotes

“…32 Berberine, with a concentration of 10 mg/mL, was found effective on Leishmaniainfected golden hamsters. 33 Other compounds such as senegalene, squamocine, and asimicine (25-100 mg/mL) isolated from Annona senegalensis Pers. showed antileishmanial effects against related promastigotes.…”

Testing of Experimental Compounds for Efficacy Against Leishmania.

“…At the indicated doses all of the compounds tested were relatively nontoxic, and with the exception of berberine itself, appeared to be less effective (structures 2,4,7,8,9) or equipotent (structures 3,5,6) in the cutaneous test system as in the visceral test system. The.two most active compounds, berberine and 8-cyanodihydroberberine, produced 56% and 46% suppression of lesion area respectively when administered at a total dose of 208 mg/kg.…”

“…Visceral leishmaniasis, the most severe type, is endemic in many areas where epidemics occur (TDR Publ., 7th Program Rpt., 2) with mortality reported to reach as high as 98 percent in untreated cases (Biagi,3;Steck,4). While it is difficult to obtain an accurate estimate of the number of human beings infected with the leishmaniases throughout the world (TDR Publ., 7th Program Rpt., 2), some estimates indicate that at least 12 million persons have one of the different forms of the disease caused by infection with these parasites (Mahmoud and Warren, 5; Croft, 6) and outbreaks often involving additional thousands of persons occur periodically (Peters, 7; TDR Publ., 7th Program Rpt., 2; Perea, 8).…”