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Integrated in silico-in vitro strategy for screening of some traditional Egyptian plants for human aromatase inhibitors.

Abstract：

ETHNOPHARMACOLOGICAL RELEVANCE:Aromatase enzyme (CYP19) is widely known as a critical target protein for treating hormone-dependent breast cancer. Natural products from traditional medicinal plants continue to be an active source of aromatase inhibitors. Meanwhile, high cost of experimental work and low hit rate associated with HTS have stimulated the implementation of in-silico virtual screening to resolve these pitfalls, where coupling of both classical wet lab procedure and VS may offer a more deepened access to bioactive compounds with less work and time waste. AIM OF THE STUDY:In this work, a sequential structure-based and ligand-based virtual screening strategy was utilized for investigating an in-house database of 1720 phytochemical constituents of 29 medicinal plants and natural products used in traditional Egyptian medicine to search for compounds with the potential to be used as inhibitors of the human aromatase enzyme. MATERIALS AND METHODS:The suggested strategy included using Glide docking with its feature 'extra precision (XP)' for carrying out structure-based virtual screening (SBVS) where the resulting hits were further promoted to ligand-based virtual screening (LBVS) through the development of two pharmacophore and QSAR models; one for steroidal and the other for non-steroidal aromatase inhibitors. RESULTS:The combined results revealed that Artemisia annua, Zingiber officinale, Cicer arietinum, Annona muricata and Vitex agnus castus were the top scoring plants in terms of in-silico activity scores, respectively. The hydro-alcoholic extracts and different solvent fractions of the top scoring plants were subsequently tested experimentally for their aromatase inhibitory activity, by the aid of in-vitro fluorometric assay. The rank ordering of the activities for the plants agreed with the ordering predicted on the basis of SBVS and LBVS workflow implemented. CONCLUSION:The suggested strategy provides a reliable means of prospecting in-silico screening of natural products databases in the search for new dug leads as aromatase inhibitors. The hits so obtained can then be subjected to further phytochemical studies, to isolate and identify suitable compounds for further in-vitro testing.

journal_name

J Ethnopharmacol

journal_title

Journal of ethnopharmacology

authors

Dawood HM,Ibrahim RS,Shawky E,Hammoda HM,Metwally AM

doi

10.1016/j.jep.2018.06.009

subject

Has Abstract

pub_date

2018-10-05 00:00:00

pages

359-372

eissn

0378-8741

issn

1872-7573

pii

S0378-8741(18)30830-4

journal_volume

224

pub_type

杂志文章

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Integrated in silico-in vitro strategy for screening of some traditional Egyptian plants for human aromatase inhibitors.