Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties

Elicitation through abiotic stress, including chemical elicitors like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metals on actinobacteria <i>Streptomyces</i> sp. SH-1312 for secondary metabolite production, with strong pharmacological activ...

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Autores principales:	Syed Shams ul Hassan, Ishaq Muhammad, Syed Qamar Abbas, Mubashir Hassan, Muhammad Majid, Hui-Zi Jin, Simona Bungau
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	natural products stress-technique actinobacteria ADMET anti-oxidant anti-cancer Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/e70edb07691d41069f3b227f6e43be3d
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spelling	oai:doaj.org-article:e70edb07691d41069f3b227f6e43be3d2021-11-11T16:54:00ZStress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties10.3390/ijms2221114321422-00671661-6596https://doaj.org/article/e70edb07691d41069f3b227f6e43be3d2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11432https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Elicitation through abiotic stress, including chemical elicitors like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metals on actinobacteria <i>Streptomyces</i> sp. SH-1312 for secondary metabolite production, with strong pharmacological activity, along with pharmacokinetics profile, was firstly investigated. The optimum metal stress conditions consisted of actinobacteria strain <i>Streptomyces</i> sp. SH-1312 with addition of mix metals (Co<sup>2+</sup> + Zn<sup>2+</sup>) ions at 0.5 mM in Gause’s medium. Under these conditions, the stress metabolite anhydromevalonolactone (MVL) was produced, which was absent in the normal culture of strain and other metals combinations. Furthermore, the stress metabolite was also evaluated for its anti-oxidant and cytotoxic activities. The compound exhibited remarkable anti-oxidant activities, recording the IC<sub>50</sub> value of 19.65 ± 5.7 µg/mL in DPPH, IC<sub>50</sub> of 15.49 ± 4.8 against NO free radicals, the IC<sub>50</sub> value of 19.65 ± 5.22 µg/mL against scavenging ability, and IC<sub>50</sub> value of 19.38 ± 7.11 µg/mL for iron chelation capacity and the cytotoxic activities against PC3 cell lines were recorded with IC<sub>50</sub> values of 35.81 ± 4.2 µg/mL after 24 h, 23.29 ± 3.8 µg/mL at 48 h, and 16.25 ± 6.5 µg/mL after 72 h. Further mechanistic studies have revealed that the compound MVL has shown its pharmacological efficacy by upregulation of P53 and BAX while downregulation of BCL-2 expression, indicating that MVL is following apoptosis in varying degrees. To better understand the pharmacological properties of MVL, in this work, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) were also evaluated. During ADMET predictions, MVL has displayed a safer profile in case of hepatotoxicity, cytochrome inhibition and also displayed as non-cardiotoxic. The compound MVL showed good binding energy in the molecular docking studies, and the results revealed that MVL bind in the active region of the target protein of P53 and BAX. This work triumphantly announced a prodigious effect of heavy metals on actinobacteria with fringe benefits as a key tool of MVL production with a strong pharmacological and pharmacokinetic profile.Syed Shams ul HassanIshaq MuhammadSyed Qamar AbbasMubashir HassanMuhammad MajidHui-Zi JinSimona BungauMDPI AGarticlenatural productsstress-techniqueactinobacteriaADMETanti-oxidantanti-cancerBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11432, p 11432 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	natural products stress-technique actinobacteria ADMET anti-oxidant anti-cancer Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	natural products stress-technique actinobacteria ADMET anti-oxidant anti-cancer Biology (General) QH301-705.5 Chemistry QD1-999 Syed Shams ul Hassan Ishaq Muhammad Syed Qamar Abbas Mubashir Hassan Muhammad Majid Hui-Zi Jin Simona Bungau Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties
description	Elicitation through abiotic stress, including chemical elicitors like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metals on actinobacteria <i>Streptomyces</i> sp. SH-1312 for secondary metabolite production, with strong pharmacological activity, along with pharmacokinetics profile, was firstly investigated. The optimum metal stress conditions consisted of actinobacteria strain <i>Streptomyces</i> sp. SH-1312 with addition of mix metals (Co<sup>2+</sup> + Zn<sup>2+</sup>) ions at 0.5 mM in Gause’s medium. Under these conditions, the stress metabolite anhydromevalonolactone (MVL) was produced, which was absent in the normal culture of strain and other metals combinations. Furthermore, the stress metabolite was also evaluated for its anti-oxidant and cytotoxic activities. The compound exhibited remarkable anti-oxidant activities, recording the IC<sub>50</sub> value of 19.65 ± 5.7 µg/mL in DPPH, IC<sub>50</sub> of 15.49 ± 4.8 against NO free radicals, the IC<sub>50</sub> value of 19.65 ± 5.22 µg/mL against scavenging ability, and IC<sub>50</sub> value of 19.38 ± 7.11 µg/mL for iron chelation capacity and the cytotoxic activities against PC3 cell lines were recorded with IC<sub>50</sub> values of 35.81 ± 4.2 µg/mL after 24 h, 23.29 ± 3.8 µg/mL at 48 h, and 16.25 ± 6.5 µg/mL after 72 h. Further mechanistic studies have revealed that the compound MVL has shown its pharmacological efficacy by upregulation of P53 and BAX while downregulation of BCL-2 expression, indicating that MVL is following apoptosis in varying degrees. To better understand the pharmacological properties of MVL, in this work, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) were also evaluated. During ADMET predictions, MVL has displayed a safer profile in case of hepatotoxicity, cytochrome inhibition and also displayed as non-cardiotoxic. The compound MVL showed good binding energy in the molecular docking studies, and the results revealed that MVL bind in the active region of the target protein of P53 and BAX. This work triumphantly announced a prodigious effect of heavy metals on actinobacteria with fringe benefits as a key tool of MVL production with a strong pharmacological and pharmacokinetic profile.
format	article
author	Syed Shams ul Hassan Ishaq Muhammad Syed Qamar Abbas Mubashir Hassan Muhammad Majid Hui-Zi Jin Simona Bungau
author_facet	Syed Shams ul Hassan Ishaq Muhammad Syed Qamar Abbas Mubashir Hassan Muhammad Majid Hui-Zi Jin Simona Bungau
author_sort	Syed Shams ul Hassan
title	Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties
title_short	Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties
title_full	Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties
title_fullStr	Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties
title_full_unstemmed	Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties
title_sort	stress driven discovery of natural products from actinobacteria with anti-oxidant and cytotoxic activities including docking and admet properties
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e70edb07691d41069f3b227f6e43be3d
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Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties

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