- In silico design, synthesis, characterization and pharmacological evaluation of captopril conjugates in the treatment of renal fibrosis
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Renal fibrosis is a renal disorder whereby production of excess fibrous connective tissue in the glomerulus and proximal convoluted tubules will occur in a reparative or reactive process leading to severe conditions like surgery, replacement, etc. Such a condition needs pharmacotherapy with drugs reducing renal overload (captopril) and inflammation (taurine). In this research project, two chemical conjugates of captopril with taurine and glutamic acid were developed using in silico analysis for an improvement in bioavailability with a reduction in inflammation. The stability of these conjugates in sheep kidney cells and in human plasma along with transport across renal cells was investigated using in vitro protocols. The results of these studies have revealed that conjugates have retained desired interactions for transportability across renal epithelial cells and their bioactivity against ACE and TGF-β. Both conjugates A and B were found to be stable over a period of 14 h in plasma and transported nearly 2 times more than captopril across renal epithelial cells. These conjugates were almost entirely hydrolyzed in renal lysosomes over a period of 14 h (87.39 ± 2.59%). Thus a combination of these two conjugates would be an effective chemotherapy to prevent progression of renal fibrosis to renal failure after in vivo studies of these conjugates.
- Jadhav, Swapnil Dashrath,Choudhari, Prafulla Balkrishna,Bhatia, Manish Sudesh
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- Exogenous hydrogen sulfide donor, and preparation and application thereof
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The invention provides an exogenous hydrogen sulfide donor, and discloses a therapeutic action of an anethol trithione derivative used as the exogenous hydrogen sulfide donor on cardiovascular diseases. The exogenous hydrogen sulfide donor can release hydrogen sulfide, can promote the growth of an HUVEC (human umbilical vein endothelial cell) atherosclerosis cell model, has an antiatherosclerotic effect, and hopefully becomes a new target drug researched and developed by drugs with antiatherosclerotic effects.
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Paragraph 0052; 0053
(2017/08/30)
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- Tetrahydroisoquinoline derivative and application thereof
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The invention belongs to the technical field of medicines, relates to a 2-{(2s)-1-[(2S)-3-ethanethioate-2-methyl propionyl] pyrrolidine-2-formamido}-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid methyl ester derivative and an application thereof, and in particular relates to a stereomer and a pharmaceutically acceptable salt of the compound. The general structural formula is as shown in the specification. The 2-{(2s)-1-[(2S)-3-ethanethioate-2-methyl propionyl] pyrrolidine-2-formamido}-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid methyl ester compound as well as pharmaceutically acceptable acid and additive salt of the compound can be combined with an existing medicine and can be individually used as an angiotensin-converting enzyme inhibitor to be applied to treatment of hypertension. Compared with the prior art, 6,7,8 side chains of a tetrahydroisoquinoline ring are obviously changed; the inhibition rate of the sample on angiotensin-converting enzyme is significantly improved; and the tetrahydroisoquinoline derivative has good application values and development and application prospects.
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Paragraph 0033; 0045
(2016/10/27)
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- Spectroscopic investigation on kinetics and mechanistic aspects to electron-transfer process into quinolinium dichromate oxidation of a high blood pressure drug captopril in acidic medium
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This study investigated on kinetics of oxidation of captopril by QDC was studied spectrophotometrically in acidic medium along with its mechanistic pathway. Such studies are greatly helpful in gaining an insight into the interaction of metal ions through the study of the mechanistic pathway of CPL in redox reactions. The oxidative product of captopril was found to be captopril disulfide was separated, and identified by FT-IR. A suitable free radical mechanism was proposed. The reaction exhibited first-order kinetics with respect to [oxidant] and fractional order in CPL. Consequently, the interaction between the complex species and CPL is supported kinetic orders of reaction by spectrophotometric verification, positive entropy of activation and the first-order rate constant increased with the increase in the dielectric constant and increase ionic strength of the medium. The reaction constants involved in the mechanism were computed and the overall activation parameters were evaluated which lend support to the proposed mechanism.
- Asiri, Abdullah M.,Khan, Aftab Aslam Parwaz,Khan, Anish
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- Synthesis and characterization of captopril derivatives
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To develop more potential angiotensin converting enzyme (ACE) inhibitors, a series of captopril (Cap) derivatives were synthesized, including Cap-glycine methyl ester, Cap-l-alanine methyl ester, Cap-l-aspartic acid dimethyl ester, Cap-l-lysine methyl ester, Cap-O-acylisourea, acetyl captopril, and benzoyl captopril. The resulting products were characterized by IR and UV-visible spectroscopy and MS, which showed the desired products were successfully synthesized. This could serve as a guide for rational design of highly potent ACE inhibitors.
- Li, He-Ping,Zhang, Juan-Juan,Qin, Long,Zhao, Ming-Dong
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p. 621 - 629
(2013/07/27)
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- Amino Acids, 15. - Diastereoselective Addition of Thiocarboxylic Acids to 1-(Methacryloyl)proline and -prolinol Derivatives
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Thiocarboxylic acids 6 adds to 1-(methacryloyl)-substituted proline and prolinol derivatives stereoselectively to give the 1-proline and -prolinol derivatives 7,7' and 9.The less soluble -diastereomers are obtained in optical yields >/= 98percent by digestion of the crude products, the configuration of which was determined by acid hydrolysis of -7,7' to (R)-3-mercapto-2-methylpropionic acid .The stereoselectivity of the additions may be explained by a seven-membered ring intermediate with an intramolecular H bridge, to which the S-nucleophiles add preferentially to give the compounds with the (2'R)-configuration. - Keywords: Amino acids/ Diastereoselective addition/ 1-(Methacryloyl)proline derivatives
- Effenberger, Franz,Isak, Heinz
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p. 553 - 560
(2007/10/02)
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