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Cisplatin (CP) is an effective chemotherapeutic agent for treatment of various types of cancer, however efforts are needed to reduce its toxic side effect. Previous studies revealed promising effect of peptides in decreasing CP induced nephrotoxicity. Herein, novel Met-based peptidomimetics were synthesized using N-acylbenzotriazole as acylating agent in high yield. Evaluation of renoprotective effect of the synthesized targets on CP treated kidney cell line (LLC-PK1) revealed that pretreatment with 1/3 IC 50 of targets II, IIIa-g attenuated CP induced cell death where the IC 50 of CP was raised from 3.28 µM to 9.25-41.1 µM. The most potent compounds IIIg, II and IIIb exhibited antioxidative stress in CP-treated LLC-PK1 cells as confirmed by raising GSH/GSSG ratio and SOD concentration as well as decreasing ROS and MDA. Additionally, in vivo experiments using Sprague Dawley rats showed renoprotective effect of IIIg against CP-induced nephrotoxicity as evidenced by improved results of renal function tests and attenuated CP-induced renal structural injury. Moreover, antioxidant activity of IIIg was demonstrated via its ability to reduce renal MDA level and up-regulate renal antioxidant element GSH level. Further, immunohistochemistry of renal specimens showed the ability of IIIg to restore CP-induced suppression of Nrf2. Interestingly, in vivo and in vitro studies demonstrated that IIIg had no effect on CP antiproliferative activity. An assessment of the ADMET properties revealed that targets IIIg, II and IIIb showed good drug-likeness in terms of their physicochemical, pharmacokinetic properties. The findings presented here showcase that IIIg is a promising renoprotective candidate with antioxidative stress potential., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Vitamin E, essential for human health, is widely used worldwide for therapeutic or dietary reasons. The differences in the metabolism and excretion of the multiple vitamin E forms are presented in this review. The important steps that influence the kinetics of each form and the distribution and processing of vitamin E forms by the liver are considered. The antioxidant as well as non-antioxidant properties of vitamin E forms are discussed. Finally, synthetic tocopherol and trolox derivatives, based on the design of multitarget directed compounds, are reviewed. It is demonstrated that selected derivatization of vitamin E or trolox structures can produce improved antioxidants, agents against cancer, cardiovascular and neurodegenerative disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

SCM-198 (Leonurine) has attracted great attention due to its cardioprotective effects in myocardial infarction (MI). However, no systematic modifications and structure-activity relationship (SAR) studies could be traced so far. In this study, 35 analogs of SCM-198 were designed, synthesized and their cardioprotective effects were evaluated. The cell viability assay on cardiomyocyte cell line H9c2 challenged with H 2 O 2 showed that several analogs exhibited more potent cytoprotective effects than SCM-198 at 1 μM and 10 μM concentrations. LDH release level in cells treated with 1 μM 14o was comparable with cells treated with 10 μM SCM-198. Results of Bcl-2 expression and caspase-3 activation accordingly indicated higher protective activity of 14o than SCM-198. Moreover, in a mouse model of MI, the mice pretreated with 14o had much lower infarct size compared with that of SCM-198. The mechanism study suggested that 14o improved cardiac morphology and reduced apoptosis of cardiomyocytes in the border zone of infarction, as proved by H&E and TUNEL staining., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

A series of vincamine derivatives were designed, synthesized and evaluated as pancreatic β-cells protective agents for type 2 diabetes mellitus. Most of the compounds displayed potent pancreatic β-cells protective activities and five derivatives were found to exhibit 20-50-fold higher activities than vincamine. Especially for compounds Vin-C01 and Vin-F03, exhibited a remarkable EC 50 value of 0.22 μM and 0.27 μM, respectively. Their pancreatic β-cells protective activities increased approximately 2 times than vincamine. In cell viability assay, compounds Vin-C01 and Vin-F03 could effectively promote β-cell survival and protect β-cells from STZ-induced apoptosis. Further cellular mechanism of action studies demonstrated that their potent β-cells protective activities were achieved by regulating IRS2/PI3K/Akt signaling pathway. The present study evidently showed that compounds Vin-C01 and Vin-F03 were two more potent pancreatic β-cells protective agents compared to vincamine and might serve as promising lead candidates for the treatment of type 2 diabetes mellitus., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Poor water solubility limits the clinical use of andrographolide and its derivatives. In an attempt to develop potent hepatoprotective drugs, a strategy was proposed to improve the aqueous solubility of andrographolide. Ten andrographolide derivatives were designed, synthesized, evaluated for aqueous solubility and in vivo hepatoprotective activity against CCl4 -induced liver injury in mice. As expected, the aqueous solubility of synthetic derivatives was effectively improved. All compounds demonstrated the effect of different degrees in improving the liver enzyme (ALT and AST) activity, especially the most promising compound 9d significantly improved liver enzyme activity, with high potency to be a new lead., (© 2013 John Wiley & Sons A/S.)

Goodyeroside A, a natural product isolated from the Goodyera species, possesses significant hepatoprotective activity and has a novel skeleton not previously observed in other synthetic drugs used for the treatment of hepatitis. Herein, we report a highly stereoselective synthesis of goodyeroside A and related analogs with varying substituents at the α position of the carbonyl group to explore the structure-activity relationships of goodyeroside A. The absolute configuration of analog 5d was confirmed by single crystal X-ray analysis. The results from in vitro and in vivo studies indicate that 5a, the fully acetylated compound of goodyeroside A, is worthy of further investigation as a lead to identify novel hepatoprotective agents.