journal
MENU ▼
Read by QxMD icon Read
search

European Journal of Medicinal Chemistry

journal
https://www.readbyqxmd.com/read/28433777/design-and-expeditious-synthesis-of-organosilanes-as-potent-antivirals-targeting-multidrug-resistant-influenza-a-viruses
#1
Yanmei Hu, Yuanxiang Wang, Fang Li, Chunlong Ma, Jun Wang
The efficacy of current influenza vaccines and small molecule antiviral drugs is curtailed by the emerging of multidrug-resistant influenza viruses. As resistance to the only FDA-approved oral influenza antiviral, oseltamivir (Tamiflu), continues to rise, there is a clear need to develop the next-generation of antiviral drugs. Since more than 95% of current circulating influenza A viruses carry the S31N mutation in their M2 genes, the AM2-S31N mutant proton channel represents an attractive target for the development of broad-spectrum antivirals...
April 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28427017/aromatase-inhibitors-and-apoptotic-inducers-design-synthesis-anticancer-activity-and-molecular-modeling-studies-of-novel-phenothiazine-derivatives-carrying-sulfonamide-moiety-as-hybrid-molecules
#2
Mostafa M Ghorab, Mansour S Alsaid, Nermin Samir, Ghada A Abdel-Latif, Aiten M Soliman, Fatma A Ragab, Dalal A Abou El Ella
Hybrid molecules are used as anticancer agents to improve effectiveness and diminish drug resistance. So, the current study aimed to introduce twenty novel phenothiazine sulfonamide hybrids 5-22, 24 and 25 of promising anticancer activity. Compounds 11 and 13 revealed more potent anticancer properties (IC50 8.1 and 8.8 μM) than that of the reference drug (doxorubicin, IC50 = 9.8 μM) against human breast cancer cell line (T47D). To determine the mechanism of their anticancer activity, compounds 5, 6, 7, 11, 13, 14, 16, 17, 19 and 22 that showed promising activity on T47D, were evaluated for their aromatase inhibitory effect...
April 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28426997/design-and-synthesis-of-neolamellarin-a-derivatives-targeting-heat-shock-protein-90
#3
Long Jiang, Ruijuan Yin, Xueting Wang, Jiajia Dai, Jing Li, Tao Jiang, Rilei Yu
In this study, we designed and synthesized a novel family of neolamellarin A derivatives that showed high inhibitory activity toward heat shock protein 90 (Hsp90), a kinase associated with cell proliferation. The 3,4-bis(catechol)pyrrole scaffold and the benzyl group with methoxy modification at N position of pyrrole are essential to the Hsp90 inhibitory activity and cytotoxicity of these compounds. Western blot analysis demonstrated that these compounds induced dramatic depletion of the examined client proteins of Hsp90, and accelerated cancer cell apoptosis...
April 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28426995/antibacterial-activity-of-n-methylbenzofuro-3-2-b-quinoline-and-n-methylbenzoindolo-3-2-b-quinoline-derivatives-and-study-of-their-mode-of-action
#4
Ning Sun, Ruo-Lan Du, Yuan-Yuan Zheng, Bao-Hua Huang, Qi Guo, Rui-Fang Zhang, Kwok-Yin Wong, Yu-Jing Lu
The emergence of multidrug-resistant bacteria causes an urgent need for new generation of antibiotics, which may have a different mechanism of inhibition or killing action from the existing. Targeting at the inhibition of bacterial cell division via the control of FtsZ function is one of the effective and promising approaches. Some natural extracts from plants such as sanguinarine and berberine (analogs of pyridinium compounds) are known to alter FtsZ function. In this study, a series of novel quaternary pyridinium compounds was constructed based on the N-methylbenzofuro[3,2-b]quinoline and N-methylbenzoindolo[3,2-b]-quinoline derivatives and their antibacterial activity against nine significant pathogens was investigated using broth microdilution method...
April 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28433679/part-i-design-synthesis-and-biological-evaluation-of-novel-pyrazole-benzimidazole-conjugates-as-checkpoint-kinase-2-chk2-inhibitors-with-studying-their-activities-alone-and-in-combination-with-genotoxic-drugs
#5
Shadia A Galal, Ahmed S Abdelsamie, Samia A Shouman, Yasmin M Attia, Hamed I Ali, Ashraf Tabll, Reem El-Shenawy, Yasmine S El Abd, Mamdouh M Ali, Abeer E Mahmoud, Abeer H Abdel-Halim, Amal A Fyiad, Adel S Girgis, Hoda I El-Diwani
Activated checkpoint kinase 2 (Chk2) is a tumor suppressor as one of the main enzymes that affect the cell cycle. 2-Biarylbenzimidazoles are potent selective class of Chk2 inhibitors; the structure-based design was applied to synthesize a new series of this class with replacing the lateral aryl group by substituted pyrazoles. Ten pyrazole-benzimidazole conjugates from the best fifty candidates according to docking programs have been subjected to chemical synthesis in this study. The activities of the conjugates 5-14 as checkpoint kinase inhibitors and as antitumor alone and in combination with genotoxic drugs were evaluated...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28432946/design-and-synthesis-of-sulfonamide-substituted-diphenylpyrimidines-sfa-dppys-as-potent-bruton-s-tyrosine-kinase-btk-inhibitors-with-improved-activity-toward-b-cell-lymphoblastic-leukemia
#6
He Liu, Menghua Qu, Lina Xu, Xu Han, Changyuan Wang, Xiaohong Shu, Jihong Yao, Kexin Liu, Jinyong Peng, Yanxia Li, Xiaodong Ma
A new series of diphenylpyrimidine derivatives (SFA-DPPYs) were synthesized by introducing a functional sulfonamide into the C-2 aniline moiety of pyrimidine template, and then were biologically evaluated as potent Bruton's tyrosine kinase (BTK) inhibitors. Among these molecules, inhibitors 10c, 10i, 10j and 10k displayed high potency against the BTK enzyme, with IC50 values of 1.18 nM, 0.92 nM, 0.42 nM and 1.05 nM, respectively. In particular, compound 10c could remarkably inhibit the proliferation of the B lymphoma cell lines at concentrations of 6...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431353/discovery-of-potential-anticancer-multi-targeted-ligustrazine-based-cyclohexanone-and-oxime-analogs-overcoming-the-cancer-multidrug-resistance
#7
Gao-Feng Zha, Hua-Li Qin, Bahaa G M Youssif, Muhammad Wahab Amjad, Maria Abdul Ghafoor Raja, Ahmed H Abdelazeem, Syed Nasir Abbas Bukhari
The drug research and development nowadays is focusing on multi-target drugs. In the treatment of cancer, therapies using drugs inhibiting one numerous targets signify a novel viewpoint. In comparison with traditional therapy, multi-targeted drugs directly aim cell subpopulations which are involved in progression of tumor. The current study comprises the synthesis of 34 novel ligustrazine-containing α, β-unsaturated carbonyl-based compounds and oximes. The growth of 5 various cancer cell types was strongly inhibited by ligustrazine-containing oximes as revealed by biological evaluation...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431341/eco-friendly-synthesis-of-novel-cyanopyridine-derivatives-and-their-anticancer-and-pim-1-kinase-inhibitory-activities
#8
Khaled A M Abouzid, Ghada H Al-Ansary, Abeer M El-Naggar
Targeting Pim-1 kinase recently proved to be profitable for conquering cancer proliferation. In the current study, we report the design, synthesis and biological evaluation of two novel series of 2-amino cyanopyridine series (5a-g) and 2-oxocyanopyridine series (6a-g) targeting Pim-1 kinase. All of the newly synthesized compounds were evaluated for their in vitro anticancer activity against a panel of three cell lines, namely, the liver cancer cell line (HepG2), the colon cancer cell line (HCT-116) and the breast cancer cell line (MCF-7)...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28426996/design-synthesis-sar-discussion-in%C3%A2-vitro-and-in%C3%A2-vivo-evaluation-of-novel-selective-egfr-modulator-to-inhibit-l858r-t790m-double-mutants
#9
Haoyang Zhang, Wenkui Wu, Chao Feng, Zhaogang Liu, Enhe Bai, Xueyuan Wang, Meng Lei, Hao Cheng, Huayun Feng, Jingmiao Shi, Jia Wang, Zhao Zhang, Tao Jin, Shanshan Chen, Shihe Hu, Yongqiang Zhu
Based upon the modeling binding mode of marketed AZD9291 with T790M, a series of 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline derivatives were designed and synthesized with the purpose to overcome the drug resistance resulted from T790M/L858R double mutations. The most potent compound 8 showed excellent enzyme inhibitory activities and selectivity with sub nanomolar IC50 values for both the single L858R and double T790M/L858R mutant EGFRs, and was more than 8-fold selective for wild type EGFR. Compound 8 exhibited good microsomes stabilities and pharmacokinetic properties and lower binding affinity to hERG ion channel than AZD9291 and displayed strong antiproliferative activity against the H1975 non-small cell lung cancer (NSCLC) cells bearing T790M/L858R and in vivo anticancer efficacy in a human NSCLC (H1975) xenograft mouse model...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28433779/identification-of-new-anti-inflammatory-agents-based-on-nitrosporeusine-natural-products-of-marine-origin
#10
Satish Chandra Philkhana, Abhishek Kumar Verma, Gorakhnath R Jachak, Bibhabasu Hazra, Anirban Basu, D Srinivasa Reddy
Nitrosporeusines A and B are two recently isolated marine natural products with novel skeleton and exceptional biological profile. Interesting antiviral activity of nitrosporeusines and promising potential in curing various diseases, evident from positive data from various animal models, led us to investigate their anti-inflammatory potential. Accordingly, we planned and synthesized nitrosporeusines A and B in racemic as well as enantiopure forms. The natural product synthesis was followed by preparation of several analogues, and all the synthesized compounds were evaluated for in vitro and in vivo anti-inflammatory potential...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28433778/novel-lipid-mimetic-prodrugs-delivering-active-compounds-to-adipose-tissue
#11
Andrea Mattarei, Andrea Rossa, Veronica Bombardelli, Michele Azzolini, Martina La Spina, Cristina Paradisi, Mario Zoratti, Lucia Biasutto
Obesity and associated pathologies are a dramatically growing problem. New therapies to prevent and/or cure them are strongly needed. Adipose tissue is a logical target for pharmacological intervention, since it is now recognized to exert an important endocrine function, secreting a variety of adipokines affecting, for example, adiposity and insulin resistance. This proof of principle work focuses on the development of novel lipid-mimetic prodrugs reaching fat deposits by the same lymphatic absorption route followed by dietary triglycerides...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28433680/organocatalyzed-and-mechanochemical-solvent-free-synthesis-of-novel-and-functionalized-bis-biphenyl-substituted-thiazolidinones-as-potent-tyrosinase-inhibitors-sar-and-molecular-modeling-studies
#12
Sadaf Mutahir, Muhammad Asim Khan, Islam Ullah Khan, Muhammad Yar, Muhammad Ashraf, Sidra Tariq, Ren-Long Ye, Bao-Jing Zhou
Eluding the involvement of solvents in organic synthesis and introducing environment friendly procedures can control environmental problems. A facile and an efficient solvent free mechanochemical method (grinding) is achieved to synthesize novel bis-biphenyl substituted thiazolidinones using non-toxic and cheap N-acetyl glycine (NAG). Organocatalytic condensation of a series of Schiff's bases bearing different substituents with thioglycolic acid produces a variety of thiazolidinones derivatives in good to excellent yield...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431354/first-example-of-peptides-targeting-the-dimer-interface-of-leishmania-infantum-trypanothione-reductase-with-potent-in%C3%A2-vitro-antileishmanial-activity
#13
Marta Ruiz-Santaquiteria, Pedro A Sánchez-Murcia, Miguel A Toro, Héctor de Lucio, Kilian Jesús Gutiérrez, Sonia de Castro, Filipa A C Carneiro, Federico Gago, Antonio Jiménez-Ruiz, María-José Camarasa, Sonsoles Velázquez
A series of 9-mer and 13-mer amide-bridged cyclic peptides derived from the linear prototype Ac-PKIIQSVGIS-Nle-K-Nle-NH2 (Toro et al. ChemBioChem2013) has been designed and synthesized by introduction of the lactam between amino acid side chains that are separated by one helical turn (i, i+4). All of these compounds were tested in vitro as both dimerization and enzyme inhibitors of Leishmania infantum trypanothione reductase (Li-TryR). Three of the 13-mer cyclic peptide derivatives (3, 4 and 6) inhibited the oxidoreductase activity of Li-TryR in the low micromolar range and they also disrupted enzyme dimerization...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431340/first-macrocyclic-3-rd-generation-alk-inhibitor-for-treatment-of-alk-ros1-cancer-clinical-and-designing-strategy-update-of-lorlatinib
#14
REVIEW
Sulman Basit, Zaman Ashraf, Kwangho Lee, Muhammad Latif
Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to 2(nd)-generation ALK inhibitors. Lorlatinib (PF-06463922) (6) is a 3(rd)-generation macrocyclic ALK-TKI that demonstrates many advantages over 2(nd)-generation ALK inhibitors. Lorlatinib has demonstrated decent kinase selectivity, promising pharmacokinetic profile, selective brain-penetration and strong antiproliferative activity in several ALK/ROS1-driven tumor models. The current review describes the activity spectrum, key events from discovery to clinical applications and the evidences that lorlatinib acts as an ALK/ROS1 inhibitor in clinical settings...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28427016/synthesis-and-in%C3%A2-vitro-antitumour-activity-of-crassalactone-d-its-stereoisomers-and-novel-cinnamic-ester-derivatives
#15
Ivana Kovačević, Mirjana Popsavin, Goran Benedeković, Jelena Kesić, Vesna Kojić, Dimitar Jakimov, Tatjana Srdić-Rajić, Gordana Bogdanović, Vladimir Divjaković, Velimir Popsavin
Naturally occurring styryl lactone, crassalactone D (1), unnatural 4-epi-crassalactone D (2), and the corresponding 7-epimers (3 and 4) have been synthesized starting from d-glucose. The key step of the synthesis is a new one-pot sequence that commenced with a Z-selective Wittig olefination of suitably functionalized sugar lactols with a stabilized ylide, (methoxycarbonylmethylene)-triphenylphosphorane, in dry methanol, to afford 1 or 3, in the mixtures with the corresponding 4-epimers (2 or 4, respectively)...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28419928/design-synthesis-and-biological-evaluation-of-3-substituted-2-oxindole-hybrid-derivatives-as-novel-anticancer-agents
#16
Romeo Romagnoli, Pier Giovanni Baraldi, Filippo Prencipe, Paola Oliva, Stefania Baraldi, Maria Kimatrai Salvador, Luisa Carlota Lopez-Cara, Roberta Bortolozzi, Elena Mattiuzzo, Giuseppe Basso, Giampietro Viola
The 2-oxindole nucleus is the central core to develop new anticancer agents and its substitution at the 3-position can effect antitumor activity. Utilizing a pharmacophore hybridization approach, a novel series of antiproliferative agents was obtained by the modification of the structure of 3-substituted-2-oxindole pharmacophore by the attachment of the α-bromoacryloyl moiety, acting as a Michael acceptor, at the 5-position of 2-oxindole framework. The impact of the substituent at the 3-position of 2-oxindole core on the potency and selectivity against a panel of seven different cancer cell lines was examined...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28419927/synthesis-and-evaluation-of-anti-plasmodial-and-cytotoxic-activities-of-epoxyazadiradione-derivatives
#17
P Ashok Yadav, Ch Pavan Kumar, Bandi Siva, K Suresh Babu, Aparna Devi Allanki, Puran Singh Sijwali, Nishant Jain, A Veerabhadra Rao
Epoxyazadiradione (1), a major compound derived from Neem oil, showed modest anti-plasmodial activity against CQ-resistant and CQ-sensitive strains of the most virulent human malaria parasite P. falciparum. A series of analogues were synthesized by modification of the key structural moieties of this high yield natural product. Out of the library of all compounds tested, compounds 3c and 3g have showed modest anti-plasmodial activity against CQ-sensitive (IC50 2.8 ± 0.29 μM and 1.5 ± 0.01 μM) and CQ-resistant strains (IC50 1...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28419930/design-synthesis-and-anticancer-potential-of-nsc-319745-hydroxamic-acid-derivatives-as-dnmt-and-hdac-inhibitors
#18
Zigao Yuan, Qinsheng Sun, Dan Li, Shuangshuang Miao, Shaopeng Chen, Lu Song, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) are important epigenetic targets during anticancer drug development. Recent study indicates that DNMT inhibitors and HDAC inhibitors display synergistic effects in certain cancers, therefore, development of molecules targeting both DNMT and HDAC is of therapeutic advantage against these cancers. Based on the structure of DNMT inhibitor NSC-319745 and the pharmacophore characteristics of HDAC inhibitors, a series of hydroxamic acid derivatives of NSC-319745 were designed and synthesized as DNMT and HDAC multifunctional inhibitors...
April 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28415012/discovery-of-2-4-6-dimethylpyrimidin-2-yl-thio-n-phenylacetamide-derivatives-as-new-potent-and-selective-human-sirtuin-2-inhibitors
#19
Lingling Yang, Xiaobo Ma, Chen Yuan, Yanying He, Ling Li, Sha Fang, Wei Xia, Tao He, Shan Qian, Zhihong Xu, Guobo Li, Zhouyu Wang
Human sirtuin 2 (SIRT2) plays pivotal roles in multiple biological processes such as cell cycle regulation, autophagy, immune and inflammatory responses. Dysregulation of SIRT2 was considered as a main aspect contributing to several human diseases, including cancer. Development of new potent and selective SIRT2 inhibitors is currently desirable, which may provide a new strategy for treatment of related diseases. Herein, a structure-based optimization approach led to new 2-((4,6-dimethylpyrimidin-2-yl)thio)-N-phenylacetamide derivatives as SIRT2 inhibitors...
April 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28415011/design-and-synthesis-of-novel-xanthine-derivatives-as-potent-and-selective-a2b-adenosine-receptor-antagonists-for-the-treatment-of-chronic-inflammatory-airway-diseases
#20
Sujay Basu, Dinesh A Barawkar, Vidya Ramdas, Meena Patel, Yogesh Waman, Anil Panmand, Santosh Kumar, Sachin Thorat, Minakshi Naykodi, Arnab Goswami, B Srinivasa Reddy, Vandna Prasad, Sandhya Chaturvedi, Azfar Quraishi, Suraj Menon, Shalini Paliwal, Abhay Kulkarni, Vikas Karande, Indraneel Ghosh, Syed Mustafa, Siddhartha De, Vaibhav Jain, Ena Ray Banerjee, Sreekanth R Rouduri, Venkata P Palle, Anita Chugh, Kasim A Mookhtiar
Adenosine induces bronchial hyperresponsiveness and inflammation in asthmatics through activation of A2B adenosine receptor (A2BAdoR). Selective antagonists have been shown to attenuate airway reactivity and improve inflammatory conditions in pre-clinical studies. Hence, the identification of novel, potent and selective A2BAdoR antagonist may be beneficial for the potential treatment of asthma and Chronic Obstructive Pulmonary Disease (COPD). Towards this effort, we explored several prop-2-ynylated C8-aryl or heteroaryl substitutions on xanthine chemotype and found that 1-prop-2-ynyl-1H-pyrazol-4-yl moiety was better tolerated at the C8 position...
April 12, 2017: European Journal of Medicinal Chemistry
journal
journal
24926
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"