Abstract

Withanolides constitute one of the most interesting classes of natural products due to their diversity of structures and biological activities. Our recent studies on withanolides obtained from plants of Solanaceae including Withania somnifera and a number of Physalis species grown under environmentally controlled aeroponic conditions suggested that this technique is a convenient, reproducible, and superior method for their production and structural diversification. Investigation of aeroponically grown Physalis coztomatl afforded 29 withanolides compared to a total of 13 obtained previously from the wild-crafted plant and included 12 new withanolides, physacoztolides I−M (9–13), 15α-acetoxy-28-hydroxyphysachenolide C (14), 28-oxophysachenolide C (15), and 28-hydroxyphysachenolide C (16), 5α-chloro-6β-hydroxy-5,6-dihydrophysachenolide D (17), 15α-acetoxy-5α-chloro-6β-hydroxy-5,6-dihydrophysachenolide D (18), 28-hydroxy-5α-chloro-6β-hydroxy-5,6-dihydrophysachenolide D (19), physachenolide A-5-methyl ether (20), and 17 known withanolides 3–5, 8, and 21–33. The structures of 9–20 were elucidated by the analysis of their spectroscopic data and the known withanolides 3–5, 8, and 21–33 were identified by comparison of their spectroscopic data with those reported. Evaluation against a panel of prostate cancer (LNCaP, VCaP, DU-145, and PC-3) and renal carcinoma (ACHN) cell lines, and normal human foreskin fibroblast (WI-38) cells revealed that 8, 13, 15, and 17–19 had potent and selective activity for prostate cancer cell lines. Facile conversion of the 5,6-chlorohydrin 17 to its 5,6-epoxide 8 in cell culture medium used for the bioassay suggested that the cytotoxic activities observed for 17–19 may be due to in situ formation of their corresponding 5β,6β-epoxides, 8, 27, and 28.

Highlights

  • Withanolides, a class of polyoxygenated steroidal lactones frequently encountered in plants of the family Solanaceae [1], are known to exhibit a variety of biological activities including cytotoxic, anti-feedant, insecticidal, trypanocidal, leishmanicidal, antimicrobial, anti-inflammatory, phytotoxic, cholinesterase inhibitory and immune-regulatory activities, and the effects on neurite outgrowth and synaptic reconstruction [2,3]

  • We have investigated the use of an environmentally controlled aeroponic cultivation technique for the production of biomass of some plants of Solanaceae and their constituent withanolides

  • Compared with the well-known hydroponic technique which utilizes a nutrient solution flowing over or in constant contact with the plant roots, the aeroponic cultivation technique constitutes a modified hydroponic technique in which the nutrient medium is intermittently sprayed on the roots which are suspended in air enclosed in an aeroponic chamber [6]

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Summary

Introduction

Withanolides, a class of polyoxygenated steroidal lactones frequently encountered in plants of the family Solanaceae [1], are known to exhibit a variety of biological activities including cytotoxic, anti-feedant, insecticidal, trypanocidal, leishmanicidal, antimicrobial, anti-inflammatory, phytotoxic, cholinesterase inhibitory and immune-regulatory activities, and the effects on neurite outgrowth and synaptic reconstruction [2,3]. Plant-based NPs are obtained from plant biomass produced by conventional cultivation in soil and/or wild-crafting Both these methods are susceptible to unanticipated environmental catastrophes and suffer from disadvantages as the former is labor intensive and is costly in land and water usage and the latter may lead to nonsustainable excessive harvesting causing ecological damage to their natural environment. To overcome these disadvantages, we have investigated the use of an environmentally controlled aeroponic cultivation technique for the production of biomass of some plants of Solanaceae and their constituent withanolides. Aeroponic systems have been used for the production of food crops [11,12,13,14] and medicinal plants [9], Molecules 2022, 27, x FOR PEER REVaIEnWd its potential for improving production of high-value phyto-pharmaceuticals has3boefe2n0 suggested [8], to the best of our knowledge this technique has not been exploited for the production of plant secondary metabolites prior to our recent report on the efficient production omf aajoprowteintthiaanl polriod-edsru(1g–8o,fFwigituhraefe1r)ionbAta(i1n)e,dnafrmomelyth2e,3b-dioimhyadsrsoowf itthheaafeerrionpAon-3icβa-lOly-sgurlofawten (p2l)a(nFtisguwrieth1)t,hbeywaielrdo-phoanrviceasltleydgarnodw/norWsoitihl-acnuialtisvoamtnedifeprala(nStosl.anaceae) [15,16]

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