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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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/21/11432 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T06:03:08Z |
| format | Article |
| id | doaj.art-e70edb07691d41069f3b227f6e43be3d |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:03:08Z |
| publishDate | 2021-10-01 |
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| spelling | doaj.art-e70edb07691d41069f3b227f6e43be3d2023-11-22T20:52:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211143210.3390/ijms222111432Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET PropertiesSyed Shams ul Hassan0Ishaq Muhammad1Syed Qamar Abbas2Mubashir Hassan3Muhammad Majid4Hui-Zi Jin5Simona Bungau6Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaDepartment of Pharmacy, Sarhad University of Science and Technology, Peshawar 25000, PakistanInstitute of Molecular Biology and Biotechnology, The University of Lahore, Lahore 54000, PakistanDepartment of Pharmacy, Capital University of Science and Technology, Islamabad 44000, PakistanShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaDepartment of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, RomaniaElicitation 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.https://www.mdpi.com/1422-0067/22/21/11432natural productsstress-techniqueactinobacteriaADMETanti-oxidantanti-cancer |
| spellingShingle | 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 International Journal of Molecular Sciences natural products stress-technique actinobacteria ADMET anti-oxidant anti-cancer |
| title | 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_short | 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 |
| topic | natural products stress-technique actinobacteria ADMET anti-oxidant anti-cancer |
| url | https://www.mdpi.com/1422-0067/22/21/11432 |
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