Abstract

  Most pharmaceutical companies have access to many untested libraries of compounds. Virtual in silico testing of these large libraries are limited to the quality of known data and even then, would fail to discover new classes of compounds. Therefore, testing in vitro in the laboratory is still very important. However, the cost of screening large libraries for existing and new biological target or properties may not be cost effective without initial leads. The aim of this study was to evaluate 90 steroidal compounds, utilizing various rapid and relatively cheap spectrophotometric testing methods. The assays used were to detect antioxidant, antifungal and inhibition activity of CYP3A4 by using 96-well microplate methods. The rationale for choosing these assays was that steroids are known to possess such activities and that the library of steroids used have quite variable structures. This may find new or enhanced potencies for these targets. The methods used was the ABTS and DPPH antioxidant assays, antimicrobial zone of inhibition testing on agar, and inhibition screening using CYP3A4 with the fluorescent substrate DBF. The main observations from the study were that several of the compounds possessed relative activities. Antioxidant assays both using ABTS and DPPH found 2 - 3 compounds with parity or better antioxidant activity (compounds 51, 77 and 81) than the control Trolox. Having a few exceptions, most of the test compounds had some scavenging antioxidant activity. For antifungal activity via yeast growth inhibition (compounds 80- and 86-mm zones of inhibition). CYP3A4 inhibition IC₅₀ values were (56.20, 710.9, 337536, 201.3, 458.9, 10.53, 160.1, and the control IC₅₀ ketoconazole was found to be less than 3.125 μM). These initial findings suggest that the above shortlisted steroidal samples may have in vivo activities as antioxidants, antifungal agents and as agents of drug-drug interactions via CYP3A4. The next step would be to obtain further analogues of the shortlist to see if potency can be increased and ideally full structural-activity relationships can be obtained to improve in silico testing. It is worthy to note that many of these compounds have limited solubility in the mostly aqueous assay conditions further conjugation with salts may also improve potencies.

Keywords: Steroids; Antioxidants; ABTS and DPPH Assays; CYP3A4; Drug-drug Interactions

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Citation

Citation: Dhvani H Kuntawala., et al. “Finding the Biological Properties from a Library of Steroids". Acta Scientific Biotechnology 1.11 (2020): 04-21.

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Copyright: © 2020 Dhvani H Kuntawala., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.