ChemInform Abstract: Exploiting Enzyme Selectivity for the Synthesis of Biologically Active Compounds

ChemInform ◽  
2010 ◽  
Vol 23 (8) ◽  
pp. no-no
Author(s):  
A. L. MARGOLIN
Keyword(s):  
Biologically Active Compounds ◽  
Biologically Active ◽  
Active Compounds ◽  
Enzyme Selectivity

Nickel(0)-Catalyzed Linear-Selective Hydroarylation of Unactivated Alkenes and Styrenes with Arylboron Acids

2018 ◽  
Author(s):  
Honggui Lv ◽  
Li-Jun Xiao ◽  
Dongbing Zhao ◽  
Qi-Lin Zhou
Keyword(s):  
Butyric Acid ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Active Compounds ◽  
Highly Efficient ◽  
Organoboronic Acids

Herein, we realized the first linear-selective hydroarylation of unactivated alkenes and styrenes with organoboronic acids by introducing directing groupon alkenes. Our method is highly efficient and scalable, and provides a modular route to assemble structurally diverse alkylarenes, especially for γ-aryl butyric acid derivatives, which have been widely utilized as chemical feedstocks to access multiple marketed drugs, and biologically active compounds.<br>

SOME DIRECTIONS IN THE MODIFICATION OF AZOLES

2020 ◽  
Vol 5 (443) ◽  
pp. 85-91
Author(s):  
Ibrayev M.K., ◽  
◽  
Takibayeva A.T., ◽  
Fazylov S.D., ◽  
Rakhimberlinova Zh.B., ◽  
...  
Keyword(s):  
13C Nmr Spectroscopy ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Active Compounds ◽  
Synthesis Conditions ◽  
Alkaloid Cytisine ◽  
Azole Ring ◽  
Cyclic Compounds ◽  
New Compounds ◽  
Derivatives Of

This article presents studies on the targeted search for new derivatives of azoles, such as benzthiazole, 3,5-dimethylpyrazole, 1,3,4-oxadiazole-2-thione, 1,3,4-thiadiazole. The possibility of combining in one molecule of the azole ring with other cyclic compounds: the alkaloid cytisine, morpholine, furan and some arenes has been studied. To obtain new compounds, the reactions of bromination, acylation, and interaction with isothiocyanates were studied. Optimal synthesis conditions were studied for all reactions. It was found that the reaction of 4-bromo-3,5-dimethylpyrazole with isothiocyanates, in contrast to the previously written derivatives of anilines, takes a longer time and requires heating the reaction mixture. The combination of a pirasol fragment with halide substituents often results in an enhanced therapeutic effect. The synthesized 2-bromine-N-(6-rodanbenzo[d]thiazole-2-yl)acetamide, due to the alkylbromide group, is an important synth in the synthesis of new benzthiazole derivatives. Its derivatives combine in one molecule the rest of rhodanbenzthiazole with alkaloid cytisine and biogenic amine morpholine and are potentially biologically active compounds, since the molecule structure contains several pharmacophoric fragments: benzthiazole and alkaloid (amine) heterocycles, rhodane and urea groups. The mechanism of formation of 1,3,4-oxadiazole-2-tyons from hydrazides under action on them by carbon disulfide was studied and assumed. It was shown that dithiocarbamates in acidic medium decompose with the release of hydrogen sulfide and the formation of highly reactive isothiocyanate group. Then, intra-molecular cyclization occurs, with the formation of end products - 1,3,4-oxadiazole-2-thions. The structures of the synthesized compounds were studied by 1H and 13C NMR spectroscopy. All synthesized substances are potentially biologically active compounds, since they contain several pharmacophore fragments in their structure.

Lactoferrin in Bone Tissue Regeneration

2020 ◽  
Vol 27 (6) ◽  
pp. 838-853 ◽  
Author(s):  
Madalina Icriverzi ◽  
Valentina Dinca ◽  
Magdalena Moisei ◽  
Robert W. Evans ◽  
Mihaela Trif ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Cells ◽  
Bone Diseases ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Bone Tissue Regeneration ◽  
Bone Homeostasis ◽  
Active Compounds

: Among the multiple properties exhibited by lactoferrin (Lf), its involvement in bone regeneration processes is of great interest at the present time. A series of in vitro and in vivo studies have revealed the ability of Lf to promote survival, proliferation and differentiation of osteoblast cells and to inhibit bone resorption mediated by osteoclasts. Although the mechanism underlying the action of Lf in bone cells is still not fully elucidated, it has been shown that its mode of action leading to the survival of osteoblasts is complemented by its mitogenic effect. Activation of several signalling pathways and gene expression, in an LRPdependent or independent manner, has been identified. Unlike the effects on osteoblasts, the action on osteoclasts is different, with Lf leading to a total arrest of osteoclastogenesis. : Due to the positive effect of Lf on osteoblasts, the potential use of Lf alone or in combination with different biologically active compounds in bone tissue regeneration and the treatment of bone diseases is of great interest. Since the bioavailability of Lf in vivo is poor, a nanotechnology- based strategy to improve the biological properties of Lf was developed. The investigated formulations include incorporation of Lf into collagen membranes, gelatin hydrogel, liposomes, loading onto nanofibers, porous microspheres, or coating onto silica/titan based implants. Lf has also been coupled with other biologically active compounds such as biomimetic hydroxyapatite, in order to improve the efficacy of biomaterials used in the regulation of bone homeostasis. : This review aims to provide an up-to-date review of research on the involvement of Lf in bone growth and healing and on its use as a potential therapeutic factor in bone tissue regeneration.

Diverse thiophenes as scaffolds in anti-cancer drug development: A concise review

2020 ◽  
Vol 20 ◽  
Author(s):  
Neha V. Bhilare ◽  
Pratibha B. Auti ◽  
Vinayak S. Marulkar ◽  
Vilas J. Pise
Keyword(s):  
Drug Development ◽  
Anticancer Agents ◽  
Heterocyclic Ring ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Cancer Drug ◽  
Active Compounds ◽  
Natural Origin ◽  
Concise Review ◽  
Anti Cancer

: Thiophenes are one among the abundantly found heterocyclic ring systems in many biologically active compounds. Moreover various substituted thiophenes exert numerous pharmacological actions on account of their isosteric resemblance with compounds of natural origin thus rendering them with diverse actions like antibacterial, antifungal, antiviral, anti-inflammatory, analgesic, antiallergic, hypotensives etc.. In this review we specifically explore the chemotherapeutic potential of variety of structures consisting of thiophene scaffolds as prospective anticancer agents.

New Potential Biologically Active Compounds: Synthesis and Characterization of Urea and Thiourea Derivativpes Bearing 1,2,4-oxadiazole Ring

2020 ◽  
Vol 17 (7) ◽  
pp. 525-534 ◽  
Author(s):  
Nevin Arıkan Ölmez ◽  
Faryal Waseer
Keyword(s):  
Microwave Irradiation ◽  
Room Temperature ◽  
Antimicrobial Activities ◽  
Phenyl Isocyanate ◽  
Single Step ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Active Compounds ◽  
Thiourea Derivatives ◽  
Acyl Chlorides

Background: Urea, thiourea, and 1,2,4-oxadiazole compounds are of great interest due to their different activities such as anti-inflammatory, antiviral, analgesic, fungicidal, herbicidal, diuretic, antihelminthic and antitumor along with antimicrobial activities. Objective: In this work, we provide a new series of potential biologically active compounds containing both 1,2,4-oxadiazole and urea/thiouprea moiety. Materials and Methods: Firstly, 5-chloromethyl-3-aryl-1,2,4-oxadiazoles (3a-j) were synthesized from the reaction of different substituted amidoximes (2a-j) and chloroacetyl chloride in the presence of pyridine by conventional and microwave-assisted methods. In the conventional method, 1,2,4-oxadiazoles were obtained in two steps. O-acylamidoximes obtained in the first step at room temperature were heated in toluene for an average of one hour to obtain 1,2,4-oxadiazoles. The yields varied from 70 to 96 %. 1,2,4-oxadiazoles were obtained under microwave irradiation in a single step in a 90-98 % yield at 160 °C in five minutes. 5-aminomethyl-3-aryl-1,2,4- oxadiazoles (5a-j) were obtained by Gabriel amine synthesis in two steps from corresponding 5-chloromethyl-3- aryl-1,2,4-oxadiazoles. Finally, twenty new urea (6a-j) and thiourea (7a-j) compounds bearing oxadiazole ring were synthesized by reacting 5-aminomethyl-3-aryl-1,2,4-oxadiazoles with phenyl isocyanate and isothiocyanate in tetrahydrofuran (THF) at room temperature with average yields (40-70%). Results and Discussions: An efficient and rapid method for the synthesis of 1,2,4-oxadiazoles from the reaction of amidoximes and acyl halides without using any coupling reagent under microwave irradiation has been developed, and twenty new urea/thiourea compounds bearing 1,2,4-oxadiazole ring have been synthesized and characterized. Conclusion: We have synthesized a new series of urea/thiourea derivatives bearing 1,2,4-oxadiazole ring. Also facile synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from amidoximes and acyl chlorides under microwave irradiation was reported. The compounds were characterized using FTIR, 1H NMR, 13C NMR, and elemental analysis techniques.

The influence of taurine and L-carnitine on 6 β-hydroxycortisol/cortisol ratio in human urine of healthy volunteers

2019 ◽  
Vol 34 (3) ◽  
Author(s):  
Anna A. Makhova ◽  
Eugenia V. Shikh ◽  
Tatiana V. Bulko ◽  
Zhanna M. Sizova ◽  
Victoria V. Shumyantseva
Keyword(s):  
Catalytic Activity ◽  
Healthy Volunteers ◽  
Human Urine ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Metabolic Ratio ◽  
Urine Samples ◽  
Cyp3a4 Activity ◽  
Active Compounds ◽  
Cortisol Ratio

Abstract Background Cytochrome P450s (CYPs, EC 1.14.14.1) are the main enzymes of drug metabolism. The functional significance of CYPs also includes the metabolism of foreign chemicals and endogenic biologically active compounds. The CYP3A4 isoform contributes to the metabolism of about half of all marketed medicinal preparations. The aim of this study was to investigate the effects of two biologically active compounds: 2-aminoethane-sulfonic acid (taurine) and 3-hydroxy-4-trimethylaminobutyrate (L-carnitine) on urinary 6β-hydroxycortisol/cortisol (6β-OHC/cortisol) metabolic ratio as a biomarker of the CYP3A4 activity of healthy volunteers. Taurine is used for the treatment of chronic heart failure and liver disease. Cardiologists, nephrologists, neurologists, gerontologists in addition to the main etiopathogenetic therapies, use L-carnitine. The quantification of the 6β-OHC/cortisol metabolic ratio as a biomarker of CYP3A4 activity in human urine was used for the assessment of CYP3A4 catalytic activity as a non-invasive test. Methods The study included 18 healthy male volunteers (aged from 18 to 35 years old). The volunteers took taurine in a dose of 500 mg twice a day or L-carnitine in a dose of 2.5 mL 3 times a day for 14 consecutive days. The test drug was given 20 min before meals. The collection of urine samples was performed before and after 3, 7, 10, and 14 days after taurine intake. The metabolic ratio of 6β-OHC/cortisol in morning spot urine samples was studied by the liquid chromatography/mass spectroscopy (LC/MS) method. Results The ratio of 6-6β-OHC/cortisol was used as a biomarker to study the taurine and L-carnitine influence on CYP3A4 metabolism of cortisol. The ratio of urinary 6β-OCH/cortisol in the morning urine samples of volunteers before the beginning of taurine therapy (baseline ratio) was 2.71 ± 0.2. Seven days after the administration of taurine in a dose of 500 mg twice a day, the 6β-OCH/cortisol ratio was 3.3 ± 0.2, which indicated the increased catalytic activity of CYP3A4 towards cortisol. As for the L-carnitine supplementation, analysis of the 6β-OCH/cortisol ratio in the urine for 14 days did not show any significant changes in this baseline ratio, indicating the lack of L-carnitine influence on the catalytic activity of CYP3A4 to cortisol. Conclusions The results obtained demonstrated the influence of taurine on 6β-OCH/cortisol metabolic ratio as a biomarker of CYP3A4 catalytic activity to cortisol. L-carnitine did not affect the activity of CYP3A4. The lack of a clinically meaningful effect of L-carnitine was established.

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