6α-Acetoxy-7α-Hydroxy-Vouacapan Isolated from Pterodon pubescens Benth. Fruit’s with Selective Activity against Prostate Cancer Cell Line: Artifact or Natural Product?

Lloret Fc,Santos Ccj

doi:10.4172/2167-0412.1000238

Abstract

Challenges encountered in standardization of plant-derived drugs involves the determination of many parameters that implies quality control methods throughout the entire process from growing conditions to the final product. This study highlights the complexity of factors involved in the production of secondary metabolites in plants. Compound 6α-acetoxy-7α-hydroxy-vouacapan Isolated from Pterodon pubescens Benth. (Fabeacea) fruit dichloromethane extract, with in vitro cytotoxic selectivity on human prostate cancer cell line was investigated to determine if the compound is an artifact produced overtime on plant storage or is characteristic of plant genotype. The chemical composition of samples from Sao Carlos (Sao Paulo, Brazil) and Ponto Chique (Minas Gerais, Brazil) were monitored monthly during one year for geranylgeraniol, 6α-acetoxy-7α-hydroxy-vouacapan, 6α-hydroxy- 7α-acetoxy-vouacapan-17α-oate methyl ester and 6α-acetoxy-7α-hydroxy-vouacapan-17α-oate methyl ester. In vitro cytotoxicity screening against human prostate cancer cell line, evaluating total growth inhibition parameter (TGI) displayed higher selectivity and potent anticancer activity with TGI 11.43 μg mL-1 when higher 6α-acetoxy- 7α-hydroxy-vouacapan over total voaucapan ratio (3.14) was achieved. Nevertheless, 6α-acetoxy-7α-hydroxyvouacapan maintained approximately the same content throughout the year among the samples in opposition to overall voaucapan content. Samples from Sao Carlos at time zero had 26% geranylgeraniol content whereas Minas Gerais samples contained the highest content of 1.3%. Throughout the stability test geranylgeraniol concentration decreased with a straight relationship of overall increase of vouacapan content. The chemical variability data was evaluated using the statistical procedure based on Principal Component Analysis (PCA) to determine which of the extract’s components had a real impact on the in vitro antiproliferative activity. Data presented herein did not suggest that 6α-acetoxy-7α-hydroxy-vouacapan is produced as artifact overtime in storage. Further studies are needed to establish other markers involved with therapeutic activity to provide consistency of the development of products with quality, efficiency, and safety.

Highlights

Natural products have long demonstrated their important role as a rich source of new targets for drug discovery
The overall extraction yield was approximately the same ranging from 2.9-3.2% (m/m), without affecting overall 6α-acetoxy-7αhydroxy-vouacapan content among different extraction process of the same sample
Fraction 7 (10 g), containing vouacapan compounds was successively chromatographed by Column chromatography (CC) on silica-gel (70-230 mesh) (5 × 60 cm) and eluted with hexane/dichloromethane (7:3) (900-1800 mL) yielded 6α-acetoxy-7α-hydroxy-vouacapan (333 mg, 3% yield), Rf 0.75; hexane/dichloromethane (6:4) (1900-2600 mL) yielded 6α-hydroxy7α-acetoxy-vouacapan-17α-oate methyl esther and 6α-acetoxy-7αhydroxy-vouacapan-17α-oate methyl esther (990 mg, 9.9% yield), Rf 0.56; hexane/dichloromethane (2:8) (2650-3100 mL) yielded geranylgeraniol (963 mg, 9.63% yield), Rf 0.29; (3350-4100 mL) yielded 6α,7α-di-hydroxy-vouacapan-17α-oato methyl esther (1.2 g, 12% yield) Rf 0.17

Summary

Introduction

Natural products have long demonstrated their important role as a rich source of new targets for drug discovery. The huge structural diversity of natural compounds together with unique mechanism of action has prompted promising applications in the fields of medicine, pharmacy and biology [1]. Among challenges encountered in product outcome is standardization of plant inputs for the pharmaceuticals industry. Factors such as soil, climate conditions, genotypes, harvesting, and post-harvest conditions have shown to have an important affect both on chemical and biological activity. Growth control of cultivars and their processing have a straight outcome on health benefits and economic issues. Phenotypes arise from the combination of genotype together with the environment where the species is grown

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