Wishing you a very Happy Birthday | Dr. Kamil Kuca

 

Dr. Kamil Kuca serves as the Editor-in-Chief of the Journal Letters in Drug Design & Discovery

 

Dr.-Kamil-Kuca

 

K. Kuca
University of Hradec Kralove
Hradec Kralove
Czech Republic

Aims & Scope | Letters in Drug Design & Discovery

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AIMS & SCOPE

Letters in Drug Design & Discovery publishes letters, full-length/mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.

Most Accessed Articles | Identification of New Inhibitors of Mutant Isocitrate Dehydrogenase 2 through Molecular Similarity-based Virtual Screening

Journal Name: Letters in Drug Design & Discovery

Author(s): Lijun Yang, Stefan Pusch, Victoria Jennings, Tianfang Ma, Qihua Zhu, Yungen Xu, Andreas von Deimling*, Xiaoming Zha*.

 

 

 

 

Graphical Abstract:

 

Abstract:

Background: Isocitrate dehydrogenase 2 (IDH2) is an enzyme catalyzing the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid (TCA). Evidences suggest that the specific mutations in IDH2 are critical to the growth and reproduction of severe tumors especially leukemia and glioblastoma. It is found that the inhibitors of mutant IDH2 are promising anti-tumor therapeutics.

Methods: A virtual screening strategy combining molecular similarity search and molecular docking was performed in the binding site of AGI-6780. YL-16, YL-17 and YL-18 were identified as novel mutant IDH2 inhibitors for the reduction of (D)-2-hydroxyglutarate in cellular evaluation. In addition, all the three compounds showed inhibition against IDH2-R172K mutated HEK-293T cells, while weak inhibition against wide-type IDH2 (WT-IDH2) HEK-293T cells.

Results: Significantly, YL-17 showed 84.55% inhibitory activity against IDH2-R172K at 1 µM and weak cytotoxicity to wide-type IDH2 at 50 µM.

Conclusion: YL-17 was highlighted as a new mutant IDH2 inhibitor that could be further developed for therapeutic applications. To read out more, please visit: http://www.eurekaselect.com/164444/article

Most Cited Articles | Novel Trifluoromethylpyrazole Acyl Thiourea Derivatives: Synthesis, Antifungal Activity and Docking Study

Journal Name: Letters in Drug Design & Discovery

Author(s): Han Wang, Zhi-Wen Zhai, Yan-Xia Shi, Cheng-Xia Tan, Jian-Quan Weng, Liang Han, Bao-Ju Li, Xing-Hai Liu*.

 

 

 

 

Graphical Abstract:

 

Abstract:

Background: In recent years, pyrazole carboxamide derivatives possessed excellent fungicidal activity. In the process of designing new fungicides, the carboxamide group was modified in order to find novel structure pyrazole carboxamide derivatives.

Methods: Ten novel trifluoromethyl pyrazole acyl thiourea derivatives were designed and synthesized. In vivo fungicidal activities of these compounds were tested against Fusarium oxysporum, Corynespora mazei and Botrytis cinerea, respectively.

Results: Particularly compounds exhibited significant control effective at 100 mg/L. More importantly, some compounds showed the good control effective at 10 mg/L. Furthermore, docking was established to study the structure-activity relationship of the title compounds.

Conclusion: It is possible that trifluoromethylpyrazole acyl thiurea derivatives, which possess good control effective against Botrytis cinerea, may become novel lead compounds for the development of fungicides with further structure modification. To read out more, please visit: http://www.eurekaselect.com/163481/article

Open Access Articles | Antitumor Activity of Cyclodextrin-based Supramolecular Platinum Prodrug In vitro and In vivo

Journal Name: Letters in Drug Design & Discovery

Author(s): Yu-Hui Zhang, Jie Wang, Siqintana Xin, Li-Juan Wang, Xianliang Sheng*.

 

 

 

 

Graphical Abstract:

 

Abstract:

Background: Considering the limitations of cisplatin in clinical application, there is ongoing research to fabricate new platinum-containing prodrug which are highly effective to tumor cells and have low toxicity to normal cells.

Methods: In this study, a cyclodextrin-based supramolecular platinum prodrug that is 6,6’-ophenylenediseleno- bridged bis (β-cyclodextrin)s (CD) and its potassium tetrachloroplatinate(II) complex was reported. The cytotoxicity experiments were performed to evaluate the anticancer activities of supramolecular prodrug in vitro by means of MTT assay. The practical application of supramolecular prodrug in tumor treatment in vivo were evaluated using BALB/c nude mice model bearing Hela cancer cells.

Results: Compared with commercial anticancer drug cisplatin, the resultant cyclodextrin-based platinum prodrug exhibited comparative anticancer effect but with much lower toxicity side effects in vitro and in vivo.

Conclusion: The cyclodextrin-based supramolecular platinum prodrug displayed antitumor activity comparable to the commercial antitumor drug cisplatin but with lower side effects both in vitro and in vivo, implying that the two adjacent cyclodextrin cavities not merely act as desired solubilizer, but also endowed the prodrug with cell permeability through the interaction of cyclodextrin with phospholipids and cholesterol on cell membrane. To read out more, please visit: http://www.eurekaselect.com/172707/article

Animated Abstracts for Articles | Preliminary Study on the Mechanism of Carvacrol Regulating Hepatocellular Carcinoma Based on Network Pharmacology

Preliminary Study on the Mechanism of Carvacrol Regulating Hepatocellular Carcinoma Based on Network Pharmacology

Journal: Letters in Drug Design & Discovery 

AuthorPro.Lidao Bao

Objective: To predict and analyze the target of anti-Hepatocellular Carcinoma(HCC) in the active constituents of Safflower by using network pharmacology.

Methods: The active compounds of safflower were collected by TCMSP, TCM-PTD database and literature mining methods. The targets of active compounds were predicted by Swiss Target Prediction server, and the target of anti-HCC drugs was collected by DisGeNET database. The target was subjected to an alignment analysis to screen out the Carvacrol, a target of safflower against HCC. The mouse HCC model was established and treated with Carvacrol. The anti-HCC target DAPK1 and PPP2R2A were verified by Western blot and co-immunoprecipitation.

Results: A total of 21 safflower active ingredients were predicted. Carvacrol was identified as a possible active ingredient according to the five principles of drug-like medicine. According to Carvacrol’s possible targets and possible targets of HCC, three co-targets were identified, including cancer-related are DAPK1 and PPP2R2A. After 20 weeks of Carvacrol treated , Carvacrol group significantly increased on DAPK1 levels and decreased PPP2R2A levels in the model mice by Western blot. Immunoprecipitation confirmed the endogenous interaction between DAPK1 and PPP2R2A.

Conclusion: Safflower can regulate the development of HCC through its active component Carvacrol, which can affect the expression of DAPK1 and PPP2R2A proteins, and the endogenous interactions of DAPK1 and PPP2R2A proteins. To read out full article, please visit: http://www.eurekaselect.com/172163/article

New Issue | Letters in Drug Design & Discovery (Volume: 16, Issue: 6)

 

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Letters in Drug Design & Discovery publishes letters, full-length/mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.

 

Articles from the journal: Letters in Drug Design & Discovery; Volume: 16, Issue: 6

 

For details on the articles, please visit this link: http://www.eurekaselect.com/node/634/letters-in-drug-design-discovery/issue/16/2491/6/9079

AIMS & SCOPE | Letters in Drug Design & Discovery

AIMS & SCOPE

Letters in Drug Design & Discovery publishes letters, full-length/mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery. To learn more about the journal, please visit: https://benthamscience.com/journals/letters-in-drug-design-and-discovery/

 

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Most Accessed Articles | Design, Synthesis and Characterization of Novel Urolithin Derivatives as Cholinesterase Inhibitor Agents

Author(s): Maryam Norouzbahari, Emine V. Burgaz, Tugba Ercetin, Amirhossein Fallah, Alireza Foroumadi, Loghman Firoozpour, Mustafa F. Sahin, Mustafa Gazi, Hayrettin O. Gulcan*.

Journal Name: Letters in Drug Design & Discovery

Considering the limitations of current cholinesterase inhibitor drugs for the treatment of Alzheimer’s disease, there is ongoing research activities to find out alternative drug candidates. The aryl-spacer-N-benzyl pharmacophore model has been effectively utilized to design various types of cholinesterase inhibitor molecules, including donepezil. Within this research study, we have questioned the significance of the benzyl group within this pharmacophore employing the urolithin derivatives. Urolithins are benzo[c]chromene analogue metabolites of ellagitannins, abundantly found in pomegranate and berry fruits. Read out full article here: http://www.eurekaselect.com/159057

 

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Open Access Articles | Synthesis and Biological Evaluation of Some Novel Thiophene-bearing Quinazoline Derivatives as EGFR Inhibitors

Author(s): Min Zou, Bo Jin, Yanrong Liu, Huiping Chen, Zhuangli Zhang, Changzheng Zhang, Zhihong Zhao, Liyun Zheng*.

With the approval of gefitinib, erlotinib, afatinib, and osimertinib for clinical use, targeting Epidermal Growth Factor Receptor (EGFR) has been intensively pursued. Similar to most therapies, challenges related to the treatment resistance against these drugs have emerged over time, so new EGFR Tyrosine Kinase Inhibitors (TKIs) need to be developed. This study aimed to investigate the potential use of a series of thiophene-bearing quinazoline derivatives as EGFR inhibitors. We designed and synthesized nine quinazolin derivatives, among which five compounds (5e, 5f, 5g, 5h, and 5i) were reported for the first time. Read out full article here: http://www.eurekaselect.com/164334

 

Open acces

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