Sampangine metabolites

In vitro antifungal activities evaluation for sampangine metabolites demonstrated comparable activities to sampangine. However, an in vivo efficacy study revealed that SAh 2 is inactive. The antifungal activity profile of sampangine metabolites led us to conclude that metabolism per se is not the cause for the in vivo inactivity of sampangine, hence, further studies on the other pharmacokinetic parameters (bioavailability, distribution, clearance, etc.) will be necessary. 

These results indicate that sampangine metabolites have comparable activities to sampangine, which was used as a positive control. 

In vitro quantitative evaluation was accomplished using two-fold serial broth macrodilution technique [54]. The activity expressed as minimum inhibitory concentration (pg/ml). Table 5 illustrates minimum inhibitory concentration (MIC) of sampangine metabolites against C. albicans B311 and C. neoformans ATCC 52657 as compared to those of sampangine. 

Hufford and co-workers131 in a study of the metabolism of the antifungal copy-rine alkaloid sampangine, used micro-probe technology for the characterization of the alkaloid s major metabolite, which was sampangine /i-glucuronic acid (61). 

Microbial metabolism studies on sampangine have resulted in the isolation and characterization of two metabolites, sampangine-4 -0-methyl-P-glucopyranoside (SAMMl) and sampangine-P-glucopyranoside (SAMM2). 

This chapter is an account of the utilization of microbial systems to predict the mammalian metabolites of the promising antifungal agent candidate, sampangine, and two of its analogs, namely benzosampangine and 3-methoxysampangine. 

A preparative-scale biotransformation of sampangine was performed with Beauvaria bassiana ATCC 7159 using the standard two-stage fermentation procedure. This afforded a pure red metabolite (33 mg, 9.7% yield) (Fig. (5)). 

The data, thus, led us to conclude that metabolite SAMMl can be represented as 0-methylhexose conjugate of sampangine. The resonance at 8 107.6 ppm was determined from the HETCOR spectrum to be an anomeric carbon. Especially noteworthy are upfield shifts for C-4 (22.3 ppm), C-5 (11.4 ppm), C-6a (17.7 ppm) and C-7 (51.7 ppm), and H-4 (2.14 ppm) and H-5 (2.14 ppm) which indicated whatever moiety was added, it should have had a profound magnetic and electronic effect on that part (ring B and C-7 in ring C) of sampangine. 

The chronological order of both studies (microbial and mammalian) will determine the used approach (retrospective, parallel or prospective). However, in this case it is difficult to classify these studies into a distinct approach. The microbial metabolism studies were initiated after tentative information obtained from a limited mammalian metabolism study of sampangine. On the other hand, it is very important to note that complete structure elucidation of mammalian metabolites would not have been possible without the microbial metabolites having been identified first. 

Since both sampangine and benzosampangine are structurally related, it was logical to expect similar metabolites to be produced. Therefore, the glucoside of benzosampangine was highly expected. 

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