药物化学期刊(英文)最新文献_第2页

Anti-Cancer Activity and Molecular Docking of Some Pyrano[3,2‑c]quinoline Analogues 吡喃[3,2 - c]喹啉类似物的抗癌活性及分子对接

药物化学期刊(英文) Pub Date : 2020-03-05 DOI: 10.4236/ojmc.2020.101001

Abdeltawab M. Saeed, I. Abdou, A. A. Salem, Mohammad A. Ghattas, Noor Atatreh, Shaikha S. Alneyadi

{"title":"Anti-Cancer Activity and Molecular Docking of Some Pyrano[3,2‑c]quinoline Analogues","authors":"Abdeltawab M. Saeed, I. Abdou, A. A. Salem, Mohammad A. Ghattas, Noor Atatreh, Shaikha S. Alneyadi","doi":"10.4236/ojmc.2020.101001","DOIUrl":"https://doi.org/10.4236/ojmc.2020.101001","url":null,"abstract":"Quinoline analogues exhibited diversified biological activities depending on the structure type. A number of natural products with pyrano[3,2-c]quinolone structural motifs and patented chromenes were reported as promising cytotoxic agents. A molecular docking study was employed to investigate the binding and functional properties of 3-amino pyranoquinolinone 2a-c as anti-cancer agents. The three 3-amino pyranoquinolinone 2a-c showed an interesting ability to intercalate the DNA-topoisomerase complex and were able to obtain energetically favorable binding modes (−8.3 - −7.5 kcal/mol). Compound 2c containing butyl chain superiority over the other two compounds 2a-b which appeared to be involved in arene-H interactions with the two dG13 aromatic centers. The butyl chain also appeared to be immersed into a side subpocket formed by the side chains of Asn520 and Glu522 and the backbone amide of Arg503, Gly504, Lys505 and Ile506. Hence, the 3-amino pyranoquinolinone 2c used as starting material to prepare derivatives of pyrano[3,2-c]quinolone containing 1,2,4-triazine ring 4a-b which will enhance the anti-cancer activity. Pyrano[3,2-c]quinoline-2,5-diones 2a-c and 4a-b were evaluated in vitro on cell lines Ehrlich Ascites carcinoma cells (EAC), liver cancer cell line Hep-G2 and breast cancer cell line MCF-7 for the development of novel anticancer agents. The screening results revealed that compounds 4a-b were found most active candidates as anticancer agents.","PeriodicalId":68630,"journal":{"name":"药物化学期刊(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78671802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Abemaciclib, a Recent Novel FDA-Approved Small Molecule Inhibiting Cyclin-Dependant Kinase 4/6 for the Treatment of Metastatic Breast Cancer: A Mini-Review Abemaciclib, fda最近批准的用于治疗转移性乳腺癌的小分子抑制细胞周期蛋白依赖性激酶4/6:一个小型综述

药物化学期刊(英文) Pub Date : 2020-01-01 DOI: 10.4236/ojmc.2020.103007

L. Voli, J. Mamyrbekova, J. Bazureau

引用次数: 4

Triphenylmethanol Conjugates of Triptorelin as Anti-Lipid Peroxidation Prodrugs 三苯基甲醇缀合物作为抗脂质过氧化的前药

药物化学期刊(英文) Pub Date : 2019-07-26 DOI: 10.4236/OJMC.2019.93003

Samiyah Alhamed, Jawzah Alnakhli, W. Boadi, R. Beni

引用次数: 1

Synthesis and Antiproliferative Activities of Triphenylmethanol Conjugates of Leuprorelin Leuprorelin三苯基甲醇偶联物的合成及抗增殖活性研究

药物化学期刊(英文) Pub Date : 2019-06-10 DOI: 10.4236/OJMC.2019.92002

R. Beni, W. Boadi, Kaleh Karim, Jawzah Alnakhli, Samiyah Alhamed

引用次数: 0

Recent Advances in the Quest for Treatment and Management of Alzheimer and Other Dementia 阿尔茨海默病和其他痴呆症治疗和管理的最新进展

药物化学期刊(英文) Pub Date : 2019-03-13 DOI: 10.4236/OJMC.2019.91001

Sameena E. Tanwir, Ajay Kumar

引用次数: 0

Synthesis and Evaluation of Folate-Conjugated Phenanthraquinones for Tumor-Targeted Oxidative Chemotherapy. 叶酸偶联苯蒽醌类药物在肿瘤靶向氧化化疗中的合成及评价。

药物化学期刊(英文) Pub Date : 2016-03-01 Epub Date: 2016-03-11 DOI: 10.4236/ojmc.2016.61001

Ajay Kumar, Venkatesh Chelvam, Mahalingam Sakkarapalayam, Guo Li, Pedro Sanchez-Cruz, Natasha S Piñero, Philip S Low, Antonio E Alegria

{"title":"Synthesis and Evaluation of Folate-Conjugated Phenanthraquinones for Tumor-Targeted Oxidative Chemotherapy.","authors":"Ajay Kumar, Venkatesh Chelvam, Mahalingam Sakkarapalayam, Guo Li, Pedro Sanchez-Cruz, Natasha S Piñero, Philip S Low, Antonio E Alegria","doi":"10.4236/ojmc.2016.61001","DOIUrl":"https://doi.org/10.4236/ojmc.2016.61001","url":null,"abstract":"Almost all cells are easily killed by exposure to potent oxidants. Indeed, major pathogen defense mechanisms in both animal and plant kingdoms involve production of an oxidative burst, where host defense cells show an invading pathogen with reactive oxygen species (ROS). Although cancer cells can be similarly killed by ROS, development of oxidant-producing chemotherapies has been limited by their inherent nonspecificity and potential toxicity to healthy cells. In this paper, we describe the targeting of an ROS-generating molecule selectively to tumor cells using folate as the tumor-targeting ligand. For this purpose, we exploit the ability of 9,10-phenanthraquinone (PHQ) to enhance the continuous generation of H2O2 in the presence of ascorbic acid to establish a constitutive source of ROS within the tumor mass. We report here that incubation of folate receptor-expressing KB cells in culture with folate-PHQ plus ascorbate results in the death of the cancer cells with an IC50 of ~10 nM (folate-PHQ). We also demonstrate that a cleavable spacer linking folate to PHQ is significantly inferior to a noncleavable spacer, in contrast to most other folate-targeted therapeutic agents. Unfortunately, no evidence for folate-PHQ mediated tumor regression in murine tumor models is obtained, suggesting that unanticipated impediments to generation of cytotoxic quantities of ROS in vivo are encountered. Possible mechanisms and potential solutions to these unanticipated results are offered.","PeriodicalId":68630,"journal":{"name":"药物化学期刊(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34755232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Biological Activity of N-Hydroxyethyl-4-aza-2,3-didehydropodophyllotoxin Derivatives upon Colorectal Adenocarcinoma Cells. n -羟乙基-4-氮杂-2,3-二脱氢鬼臼毒素衍生物对结直肠腺癌细胞的生物活性。

药物化学期刊(英文) Pub Date : 2014-03-01 DOI: 10.4236/ojmc.2014.41001

Christian Vélez, Beatriz Zayas, Ajay Kumar

{"title":"Biological Activity of N-Hydroxyethyl-4-aza-2,3-didehydropodophyllotoxin Derivatives upon Colorectal Adenocarcinoma Cells.","authors":"Christian Vélez, Beatriz Zayas, Ajay Kumar","doi":"10.4236/ojmc.2014.41001","DOIUrl":"https://doi.org/10.4236/ojmc.2014.41001","url":null,"abstract":"Etoposide is a chemotherapy drug derived from the natural lignin podophyllotoxin. Our novel generated Aza-podophyllotoxin compounds (AZP 8a & AZP 9a) are analogues of podophyllotoxin and were previously screened for anti-cancer activity through the NCI 60 cell line screening panel showing activity on various cell types including colon cancer. This study expands the toxicological screening by studying apoptosis and various hallmark events as part of the mechanism of action of these compounds on colon cancer cells. The COLO 205 cell line was selected and exposed to AZP to determine the IC50 doses at 24 hours treatment. Apoptosis hallmark events such as migration of phosphatidylserine (PS) to the cell membrane, DNA fragmentation, cell cycle effects, mitochondrial membrane permeabilization and caspase activation were included. Experiments were performed in triplicates for all tested compounds including AZP 8a, AZP 9a, camptothecin as positive control and vehicle as negative control. Our results present contrasting apoptotic activity between the experimental compounds. Compound 8a presented migration of PS (annexin V assay), DNA fragmentation and cell cycle arrest at S phase. Compound 9a presented PS migration with fragmented DNA, cell cycle arrest at S phase, mitochondrial membrane permeabilization and activation of caspase 3, 8 and 9. Compound 8a without the oxygen atoms in ring A appears to cause effects similarly to autophagy as induced by etoposide, a cancer drug analogue of our heterocyclic compounds. Compound 9a with the oxygen atoms in expanded ring A presented induction of cell death following activation of a classical apoptosis pathway. Our results suggest that minor structural differences among these AZP can account for the difference in biological response and cancer cell toxicity.","PeriodicalId":68630,"journal":{"name":"药物化学期刊(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4236/ojmc.2014.41001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32948023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5