scholarly journals Engineering of Saccharomyces pastorianus old yellow enzyme 1 for the synthesis of pharmacologically active (S)-profen derivatives

2021 ◽  
Vol 507 ◽  
pp. 111568
Author(s):  
Guigao Liu ◽  
Shang Li ◽  
Qinghua Shi ◽  
Hengyu Li ◽  
Jiyang Guo ◽  
...  
Keyword(s):  
Old Yellow Enzyme ◽  
Saccharomyces Pastorianus ◽  
Pharmacologically Active

scholarly journals Engineering of Saccharomyces pastorianus Old Yellow Enzyme 1 for the Synthesis of Pharmacologically Active (S)-Profen Derivatives

2020 ◽  
Author(s):  
Guigao Liu ◽  
Shang Li ◽  
Qinghua Shi ◽  
Hengyu Li ◽  
Jiyang Guo ◽  
...  
Keyword(s):  
Asymmetric Reduction ◽  
Methyl Esters ◽  
Pichia Stipitis ◽  
Site Directed Mutagenesis ◽  
Old Yellow Enzyme ◽  
Saccharomyces Pastorianus ◽  
Mutation Strategy ◽  
Arylpropionic Acid ◽  
Pharmacologically Active ◽  
Key Residues

<a>2-Arylpropionic acid </a><a>derivatives</a>, such as ibuprofen, constitute an important group of non-steroidal anti-inflammatory drugs (NSAIDs). Biocatalytic asymmetric reduction of<a> 2-arylacrylic acid</a> derivatives by ene reductases (EREDs) is a valuable approach for synthesis of these derivatives. However, previous bioreduction of <a>2-arylacrylic acid derivatives</a> by either ERED wild-types or variants resulted solely in nonpharmacological (<i>R</i>)-enantiomers as the products. <a></a><a>Here, </a>we present the engineering of <i>Saccharomyces pastorianus</i> old yellow enzyme 1 (OYE1) into (<i>S</i>)-stereoselective enzymes, which afford pharmacologically active (<i>S</i>)-profen derivatives. By structural comparison of substrate recognition in related EREDs and analysis of non-covalent contacts in the pro-<i>S</i> model of OYE1, the key residues of OYE1 that switch its stereoselectivity to an (<i>S</i>)-stereopreference were identified. Systematic site-directed mutagenesis screening at these positions successfully provided the (<i>S</i>)-stereoselective OYE1 variants, which catalyzed stereoselective bioreduction of various profen precursors to afford pharmacologically active (<i>S</i>)-derivatives including (<i>S</i>)-ibuprofen and (<i>S</i>)-naproxen methyl esters with up to >99% <i>ee</i> values. <a>Moreover, the key residues and mutation strategy obtained from OYE1 </a>could be further transferred to OYE 2.6 (from <i>Pichia stipitis</i>) and KnOYE1 (from <i>Kazachstania naganishii</i>) to create the (<i>S</i>)-stereoselective EREDs. Our results may provide a generalizable strategy for stereocontrol of OYEs and set the basis for biocatalytic production of (<i>S</i>)-profens.

scholarly journals Engineering of Saccharomyces pastorianus Old Yellow Enzyme 1 for the Synthesis of Pharmacologically Active (S)-Profen Derivatives

2020 ◽  
Author(s):  
Guigao Liu ◽  
Shang Li ◽  
Qinghua Shi ◽  
Hengyu Li ◽  
Jiyang Guo ◽  
...  
Keyword(s):  
Asymmetric Reduction ◽  
Methyl Esters ◽  
Pichia Stipitis ◽  
Site Directed Mutagenesis ◽  
Old Yellow Enzyme ◽  
Saccharomyces Pastorianus ◽  
Mutation Strategy ◽  
Arylpropionic Acid ◽  
Pharmacologically Active ◽  
Key Residues

<a>2-Arylpropionic acid </a><a>derivatives</a>, such as ibuprofen, constitute an important group of non-steroidal anti-inflammatory drugs (NSAIDs). Biocatalytic asymmetric reduction of<a> 2-arylacrylic acid</a> derivatives by ene reductases (EREDs) is a valuable approach for synthesis of these derivatives. However, previous bioreduction of <a>2-arylacrylic acid derivatives</a> by either ERED wild-types or variants resulted solely in nonpharmacological (<i>R</i>)-enantiomers as the products. <a></a><a>Here, </a>we present the engineering of <i>Saccharomyces pastorianus</i> old yellow enzyme 1 (OYE1) into (<i>S</i>)-stereoselective enzymes, which afford pharmacologically active (<i>S</i>)-profen derivatives. By structural comparison of substrate recognition in related EREDs and analysis of non-covalent contacts in the pro-<i>S</i> model of OYE1, the key residues of OYE1 that switch its stereoselectivity to an (<i>S</i>)-stereopreference were identified. Systematic site-directed mutagenesis screening at these positions successfully provided the (<i>S</i>)-stereoselective OYE1 variants, which catalyzed stereoselective bioreduction of various profen precursors to afford pharmacologically active (<i>S</i>)-derivatives including (<i>S</i>)-ibuprofen and (<i>S</i>)-naproxen methyl esters with up to >99% <i>ee</i> values. <a>Moreover, the key residues and mutation strategy obtained from OYE1 </a>could be further transferred to OYE 2.6 (from <i>Pichia stipitis</i>) and KnOYE1 (from <i>Kazachstania naganishii</i>) to create the (<i>S</i>)-stereoselective EREDs. Our results may provide a generalizable strategy for stereocontrol of OYEs and set the basis for biocatalytic production of (<i>S</i>)-profens.

Laricifomes officinalis – a rich source of pharmacologically active triterpenes

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381 ◽  
Author(s):  
S Sturm ◽  
K Gallmetzer ◽  
A Friedl ◽  
B Waltenberger ◽  
V Temml ◽  
...  
Keyword(s):  
Rich Source ◽  
Pharmacologically Active

Traditional, Pharmacological and Patenting Potential of Neem (Azadirachta indica): A Review

2017 ◽  
Vol 3 (4) ◽  
pp. 383-391
Author(s):  
Mohd Asif Khan ◽  
Shashi Bhooshan Tiwari ◽  
Himanshu Gupta ◽  
Huma Noor
Keyword(s):  
Azadirachta Indica ◽  
Indian Subcontinent ◽  
National Academy Of Sciences ◽  
Neem Tree ◽  
Commercial Plant ◽  
Pharmacological Potential ◽  
Pharmacologically Active ◽  
In The Beginning ◽  
Prevention And Cure ◽  
Academy Of Sciences

Since ancient time, herbal drugs were highly used in the prevention and cure of various human illnesses. In India, Azadirachta indica being commonly known as Neem or Margosa is one of the multi-functional trees; belonging to Meliaceae family. In 1992, the US National Academy of Sciences was published a report entitled ‘Neem- a tree for solving global problems’. It is still considered as ‘village dispensary’ throughout the India. There are two species of Azadirachta which have been investigated; Azadirachta indica that is found in the Indian subcontinent and Azadirachta excelsa Kack that is homegrown to Indonesia and Philippines. A large number of pharmacologically active substances have been identified and isolated from the different parts of neem including azadirachtin, meliacin, gedunin, salanin, nimbin, valassin and various other components which are derived from these main compounds. Many different studies have been evaluated and authenticated for its various traditional and pharmacological activities like itching, leprosy, wound healing, spermicidal, anti-inflammatory, insecticidal, antidiabetic and analgesic etc. In the beginning of 1979, patenting on neem was started by CSIR to separate the active compounds from neem oil. Its great implantation fights with soil erosion, global warming, deforestations and desertification world-wide. In 2002, World Neem Conference raised the neem tree as an industrial or commercial plant. This review is going to explore comprehensively; traditional, pharmacological potential along with patenting, environmental & industrial significant of various parts of neem tree with safety concerns.

Pharmacognostical and pharmacological activity of Justicia gendarussa burm.f.: a comprehensive review

2020 ◽  
Vol 11 (3) ◽  
pp. 3384-3390
Author(s):  
Ashish ◽  
Anjali ◽  
Dixit Praveen K ◽  
Nagarajan K ◽  
Sahoo Jagannath
Keyword(s):  
Pharmacological Activity ◽  
Chemical Constituents ◽  
Biological Action ◽  
Andaman Islands ◽  
Comprehensive Review ◽  
Medicinal Value ◽  
Anti Oxidant ◽  
Phytochemical Constituents ◽  
Pharmacologically Active ◽  
Different Parts

Justicia gendarussa Burm .f. (family Acanthaceae) which is also known as willow-leaves and commonly known as Nili-Nirgundi, it is very commonly found nearby to China and its availability is very common in larger parts of India and Andaman islands. Traditionally it is used to treat various sorts of disorders such as wound healing, anti-inflammatory, anti-oxidant, antiproliferative, anti-arthritic etc. Justicia gendarussa is one of the crucial herbs which has been used in the Ayurveda. Majorly leaves parts of the plant shows the pharmacological activity but the root of the plant Justicia gendarussa is also have the important medicinal values. A large variety of pharmacologically active constituents i.e., alkaloids, flavonoids, saponin, carbohydrates, steroids, triterpenoids, carotenoids, aminoacids, tannins, phenolics, coumarines and anthaquinones are also present in this plant and they makes the plant pharmacologically important. The activity of the plant is also dependent on the solvent which is used for the extraction the various vital chemical constituents. The different- different parts of the plants having the different medicinal values also differ in the chemical values. This review is not only focused on the essential phytochemical constituents which is available in the plant but it also explains their necessary medicinal value to shows the essential biological action and phytopharmacological actions of various parts of the plant.

Development of Solid-Self Micron Emulsifying Drug Delivery Systems

2013 ◽  
Vol 6 (2) ◽  
pp. 2014-2021
Author(s):  
Preethi Sudheer ◽  
Koushik Y ◽  
Satish P ◽  
Uma Shankar M S ◽  
R S Thakur
Keyword(s):  
Drug Delivery ◽  
Systemic Circulation ◽  
Water Soluble ◽  
Future Research ◽  
Steady Increase ◽  
Liquid Form ◽  
Lipophilic Compounds ◽  
Modern Drug ◽  
Pharmaceutical Scientist ◽  
Pharmacologically Active

As a consequence of modern drug discovery techniques, there has been a steady increase in the number of new pharmacologically active lipophilic compounds that are poorly water soluble and solubility is one of the most important parameter to achieve desired concentration of drug in systemic circulation for therapeutic response. It is a great challenge for pharmaceutical scientist to convert those molecules into orally administered formulation with sufficient bioavailability.  Among the several approaches to improve oral bioavailability of these molecules, Self-micron emulsifying drug delivery system (SMEDDS) is one of the approaches usually used to improve the bioavailability of hydrophobic drugs. However, conventional SMEDDS are mostly prepared in a liquid form, which can have several disadvantages. Accordingly, solid SMEDDS (S-SMEDDS) prepared by solidification of liquid/semisolid self-micron emulsifying (SME) ingredients into powders have gained popularity. This article provides an overview of the recent advancements in S-SMEDDS such as methodology, techniques and future research directions.

Biologically Active 2,5-Disubstituted-1,3,4-Oxadiazoles

2009 ◽  
Vol 2 (1) ◽  
pp. 390-406
Author(s):  
Harish Rajak ◽  
Murli Dhar Kharya ◽  
Pradeep Mishra
Keyword(s):  
Heterocyclic Compounds ◽  
Medical Literature ◽  
Biological Activities ◽  
Biologically Active ◽  
Pharmacological Properties ◽  
Clinical Use ◽  
Synthetic Drugs ◽  
Physiologic Activity ◽  
Pharmacologically Active

There are vast numbers of pharmacologically active heterocyclic compounds in regular clinical use. The presence of heterocyclic structures in diverse types of compounds is strongly indicative of the profound effects such structure exerts on physiologic activity, and recognition of this is abundantly reflected in efforts to find useful synthetic drugs. The 1,3,4-oxadiazole nucleus has emerged as one of the potential pharmacophore responsible for diverse pharmacological properties. Medical Literature is flooded with reports of a variety of biological activities of 2,5-Disubstituted-1,3,4-oxadiazoles. The present work is an attempt to summarize and enlist the various reports published on biologically active 2,5-disubstituted-1,3,4-oxadiazoles.

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