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Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing
Lycium shawii Roem. & Schult and resin of Aloe vera (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the is...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281707/ https://www.ncbi.nlm.nih.gov/pubmed/32414030 http://dx.doi.org/10.3390/ph13050094 |
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author | Ur Rehman, Najeeb Halim, Sobia Ahsan Khan, Majid Hussain, Hidayat Yar Khan, Husain Khan, Ajmal Abbas, Ghulam Rafiq, Kashif Al-Harrasi, Ahmed |
author_facet | Ur Rehman, Najeeb Halim, Sobia Ahsan Khan, Majid Hussain, Hidayat Yar Khan, Husain Khan, Ajmal Abbas, Ghulam Rafiq, Kashif Al-Harrasi, Ahmed |
author_sort | Ur Rehman, Najeeb |
collection | PubMed |
description | Lycium shawii Roem. & Schult and resin of Aloe vera (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the isolation of 14 known compounds, viz., 1–9 from L. shawii and 10–20 from A. vera. Their structures were confirmed by combined spectroscopic techniques including 1D ((1)H and (13)C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS). The cytotoxic potential of isolates was tested against the triple-negative breast cancer cell line (MDA-MB-231). Compound 5 exhibited excellent antiproliferative activity in a range of 31 μM, followed by compounds 1–3, 7, and 12, which depicted IC(50) values in the range of 35–60 μM, while 8, 6, and 9 also demonstrated IC(50) values >72 μM. Subsequently, in silico target fishing was applied to predict the most potential cellular drug targets of the active compounds, using pharmacophore modeling and inverse molecular docking approach. The extensive in silico analysis suggests that our compounds may target carbonic anhydrase II (CA-II) to exert their anticancer activities. When tested on CA-II, compounds 5 (IC(50) = 14.4 µM), 12 (IC(50) = 23.3), and 2 (IC(50) = 24.4 µM) showed excellent biological activities in vitro. Additionally, the ethyl acetate fraction of both plants showed promising antioxidant activity. Among the isolated compounds, 4 possesses the highest antioxidant (55 μM) activity followed by 14 (241 μM). The results indicated that compound 4 can be a promising candidate for antioxidant drugs, while compound 5 is a potential candidate for anticancer drugs. |
format | Online Article Text |
id | pubmed-7281707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72817072020-06-15 Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing Ur Rehman, Najeeb Halim, Sobia Ahsan Khan, Majid Hussain, Hidayat Yar Khan, Husain Khan, Ajmal Abbas, Ghulam Rafiq, Kashif Al-Harrasi, Ahmed Pharmaceuticals (Basel) Article Lycium shawii Roem. & Schult and resin of Aloe vera (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the isolation of 14 known compounds, viz., 1–9 from L. shawii and 10–20 from A. vera. Their structures were confirmed by combined spectroscopic techniques including 1D ((1)H and (13)C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS). The cytotoxic potential of isolates was tested against the triple-negative breast cancer cell line (MDA-MB-231). Compound 5 exhibited excellent antiproliferative activity in a range of 31 μM, followed by compounds 1–3, 7, and 12, which depicted IC(50) values in the range of 35–60 μM, while 8, 6, and 9 also demonstrated IC(50) values >72 μM. Subsequently, in silico target fishing was applied to predict the most potential cellular drug targets of the active compounds, using pharmacophore modeling and inverse molecular docking approach. The extensive in silico analysis suggests that our compounds may target carbonic anhydrase II (CA-II) to exert their anticancer activities. When tested on CA-II, compounds 5 (IC(50) = 14.4 µM), 12 (IC(50) = 23.3), and 2 (IC(50) = 24.4 µM) showed excellent biological activities in vitro. Additionally, the ethyl acetate fraction of both plants showed promising antioxidant activity. Among the isolated compounds, 4 possesses the highest antioxidant (55 μM) activity followed by 14 (241 μM). The results indicated that compound 4 can be a promising candidate for antioxidant drugs, while compound 5 is a potential candidate for anticancer drugs. MDPI 2020-05-13 /pmc/articles/PMC7281707/ /pubmed/32414030 http://dx.doi.org/10.3390/ph13050094 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ur Rehman, Najeeb Halim, Sobia Ahsan Khan, Majid Hussain, Hidayat Yar Khan, Husain Khan, Ajmal Abbas, Ghulam Rafiq, Kashif Al-Harrasi, Ahmed Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing |
title | Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing |
title_full | Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing |
title_fullStr | Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing |
title_full_unstemmed | Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing |
title_short | Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing |
title_sort | antiproliferative and carbonic anhydrase ii inhibitory potential of chemical constituents from lycium shawii and aloe vera: evidence from in silico target fishing and in vitro testing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281707/ https://www.ncbi.nlm.nih.gov/pubmed/32414030 http://dx.doi.org/10.3390/ph13050094 |
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