Abstract:
BACKGROUND:Cancer is the second leading cause of death globally. Hydrazone and hydrazone derivatives have high activity, and for this reason, these compound are greatly used by researchers to synthesize new anti-cancer drug. The aim of this research work is to synthesize novel anticancer agents. METHODS:New hydrazone derivatives were synthesized via a reaction between 3-formylphenyl methyl carbonate and benzhydrazide, 4-methylbenzoic hydrazide, 4-tert-butylbenzoic hydrazide, 4-nitrobenzoic hydrazide and 3- methoxybenzoic hydrazide, and were successfully characterized using elemental analysis, 1H-NMR, 13C-NMR, FT-IR and LC-MS techniques. The synthesized compounds were evaluated for their antimicrobial (some grampositive and -negative bacteria, filamentous fungi and yeasts), anti-proliferative (T47D and HCC1428-breast cancer cells) and anti-angiogenic (HUVEC-endothelial cells) activities. The anti-proliferative activities of the hydrazone compounds R1-R5 were studied on these cell lines by MTT assay. The anti-angiogenic potential of the compounds was determined by the endothelial tube formation assay. To identify structural features related to the anti-proliferative activity of these compounds, 2D-QSAR was performed. RESULT:The results indicated that compound R3 exhibited strong anti-angiogenic and anti-proliferative activity on breast cancer cell lines and healthy cell lines. Also, this compound; possessing a tertiary butyl moiety on the hydrazine, exhibited the highest inhibitory effect against all tested microorganisms; in particular, it inhibited Candida albicans at a lower concentration than ketoconazole. Among the investigated compounds, those bearing methyl, tertiary butyl (compound R2, R3) and methoxy (compound R5) moiety were found to be more successful anticandidal derivatives than standard antifungal antibiotics. The QSAR analysis suggested that the tumor specificity of the hydrazone correlated with their molecular weight, lipophilicity, molar refractivity, water solubility, DipolHybrid:(MOPAC) and ExchangeEnergy:(MOPAC). Absorption, Distribution, Metabolism and Elimination (ADME) analysis of the hydrazone compounds showed that they have favorable pharmacokinetic and drug-likeness properties. The ADME results clarify that R3 is the best compound in terms of pharmacokinetic properties. In contrast to other compounds; target prediction analysis of the compound R3 showed inhibitory activity on estrogen-related receptor alpha transcription factor (ESRRA). The target prediction analysis was supported by molinspiration bioactivity score. CONCLUSION:The R3 compound is considered to be an important candidate for future studies with its suitability for the Lipinski's rule of five for drug-likeness, and effective in vitro and in silico results.
journal_name
Anticancer Agents Med Chemjournal_title
Anti-cancer agents in medicinal chemistryauthors
Ünver H,Berber B,Demirel R,Koparal ATdoi
10.2174/1871520619666190318125824subject
Has Abstractpub_date
2019-01-01 00:00:00pages
1658-1669issue
13eissn
1871-5206issn
1875-5992pii
ACAMC-EPUB-97394journal_volume
19pub_type
杂志文章abstract::The use of statins has scaled up to become one of the most prescribed medicines in the world and have been very useful in the manegement of cardiovascular diseases and related mortality. The disclosure of their chemical structure similar to that of hydroxy methyl glutaryl-CoA (HMG-CoA) revealed their ability to compet...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152012800228715
更新日期:2012-05-01 00:00:00
abstract::Recently, intensive laboratory and preclinical studies have identified and validated therapeutic molecular targets in cancer, particularly the receptor tyrosine kinases, the intracellular pathways, and the genetic and epigenetic alterations, resulting in an unprecedented surge of novel, targeted therapies and therapeu...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152008784533099
更新日期:2008-06-01 00:00:00
abstract::Cilengitide, a cyclic RGD pentapeptide, is currently in clinical phase III for treatment of glioblastomas and in phase II for several other tumors. This drug is the first anti-angiogenic small molecule targeting the integrins αvβ3, αvβ5 and αvβ1. It was developed by us in the early 90s by a novel procedure, the spatia...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152010794728639
更新日期:2010-12-01 00:00:00
abstract::Protein kinases are one of the largest known families of enzyme characterized by having a well conserved ATP binding pocket. Most of the synthetic kinase inhibitors are ATP-competitive, but display some potential problems, like selectivity, discrepancy between the in vitro and in vivo inhibition assays and an high ris...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152009789056930
更新日期:2009-09-01 00:00:00
abstract::Replication fork reversal and restart has gained immense interest as a central response mechanism to replication stress following DNA damage. Although the exact mechanism of fork reversal has not been elucidated precisely, the involvement of diverse pathways and different factors has been demonstrated, which are centr...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520620666200518082433
更新日期:2020-01-01 00:00:00
abstract::Colorectal cancer is a major global health problem with more than a million new cases diagnosed worldwide in 2005. In the United States, this malignancy is the third most common with 145,000 new cases and the second most lethal with 56,000 deaths in 2005. Unfortunately, preclinical diagnostic screening in the U.S. pop...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152007781668742
更新日期:2007-09-01 00:00:00
abstract::Cancer is the deadliest disease worldwide and the development of safer chemical entities to treat cancer is one of the major challenges of medicinal chemistry. Emergence of new cases every year and development of multiple drug resistance against available molecular entities has turned the focus of researchers towards ...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520620999201124212840
更新日期:2020-11-24 00:00:00
abstract::In both bacteria and eukaryotes the alkylated, oxidized, and deaminated bases and depurinated lesions are primarily repaired via an endogenous preventive pathway, i.e. base excision repair (BER). Radiation therapy and chemotherapy are two important modes of cancer treatment. Many of those therapeutic agents used in th...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152008784220366
更新日期:2008-05-01 00:00:00
abstract::The evasion of cancer cells from the induction of cell death pathways results in the resistance of tumor to current treatment modalities. Therefore, the resistance to cell death, one of the hallmarks of cancer, is a major target in the development of new approaches to selectively affect cancer cells. The complex inter...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152012802650084
更新日期:2012-10-01 00:00:00
abstract:BACKGROUND:The cause of cervical cancer can be traced to Human Papilloma Virus (HPV) along with other, nonviral factors. The uterine cervix is reactive to hormones, and female hormones have been implicated in cervical cancer pathogenesis. Previous studies have indicated that malignant cervical cells tend to lose Estrog...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520618666180830162517
更新日期:2018-01-01 00:00:00
abstract::Life expectancy has impressively increased over the past century and the US population over 65 years is rapidly growing, especially those over 80 years. In fact, persons older than 80 years have increased by more than 250% between the years 1960 and 2000, and it is expected that the population aged >75 years will trip...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/18715206113136660363
更新日期:2013-11-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDA) remains one of the deadliest types of cancers. Median survival rate is very poor with the currently available chemotherapeutical regimens. Therefore, discovery of new antineoplastic agents against PDA is one of the focused areas of contemporary research. The present study was und...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520615666150824153906
更新日期:2016-01-01 00:00:00
abstract::Compounds that can bind and stabilize non-canonical DNA structures are named quadruplex and are of interest in anticancer drug design due to their selective inhibitions of telomerase and consequent effects on cell proliferation. In this study, we report novel Co/Cu [II] complex compounds as G-quadruplex DNA binding li...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520616666160204111637
更新日期:2016-01-01 00:00:00
abstract::The article has been withdrawn at the request of the editor of the journal Anti-Cancer Agents in Medicinal Chemistry. Bentham Science apologizes to the readers of the journal for any inconvenience this may cause. Bentham Science Disclaimer:It is a condition of publication that manuscripts submitted to this journal ha...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520617666171114111053
更新日期:2017-11-13 00:00:00
abstract:BACKGROUND:Intrinsic resistance to apoptotic cell death due to co-occurrence of mutated KRAS and p53 is frequently reported in pancreatic cancer that renders them aggressive, highly proliferative and metastatic. In addition, these cancer types are less sensitive to apoptosis inducing drugs where promotion of autophagic...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Liposomes have been employed to improve pharmacokinetics and reduce side effects of drugs. They can be functionalized with antibodies for targeted delivery. While the monoclonal antibody trastuzumab has been employed in the therapy of HER2-positive breast cancer, the resistance developed during treatment has...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:To explore the cytotoxic and apoptotic activity of the pierisin-6 protein in HPV HeLa and HepG2 cell lines. METHODS:In this study, isolation, and purification of cytotoxic Prierisin-6 from the larvae of Pieris napi by affinity column chromatography techniques. Characterization of full-length mRNA of pierisi...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520619666181127113848
更新日期:2019-01-01 00:00:00
abstract::Cancer is one of the most fatal diseases in the world and it has been years that finding new drugs and chemotherapeutic techniques with lowest side effects become one of the most important challenging matters needs really hard efforts. Chlorambucil (CBL), an ancient direct-acting alkylating anticancer agent, is common...
journal_title:Anti-cancer agents in medicinal chemistry
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doi:10.2174/18715206113139990132
更新日期:2013-11-01 00:00:00
abstract:BACKGROUND:Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal bloo...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520618666181025091128
更新日期:2018-01-01 00:00:00
abstract::MicroRNAs (miRNAs) are emerging as important regulators in various pathobiological processes in cancer. Genistein, as a major isoflavonoid isolated from dietary soybean, possesses a wide variety of biological activities particularly in cancer prevention. However, the molecular mechanisms by which genistein elicits its...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/18715206113139990006
更新日期:2013-09-01 00:00:00
abstract::For thousands of years medicine and natural products have been closely linked through the use of traditional medicines and natural poisons. Mushrooms have an established history of use in traditional oriental medicine, where most medicinal mushroom preparations are regarded as a tonic, that is, they have beneficial he...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520611009050424
更新日期:2010-06-01 00:00:00
abstract::Gestational trophoblastic neoplasia is a rare malignancy, which can occur after any type of pregnancy. The incidence varies according to the geographical location and ethnic origin. Although most patients with gestational trophoblastic neoplasia are cured by conventional chemotherapy and surgery, some suffer resistant...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152010790909317
更新日期:2010-02-01 00:00:00
abstract::β-Glucans are polysaccharides of β-D-glucose extracted from the cell walls of different species of mushrooms, yeast, oat, barley, seaweeds, algae and bacteria. Modern biomedical research has identified β-glucans as biological response modifiers (BRM) with anti-tumor properties that elicit potent immune responses throu...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520611313050003
更新日期:2013-06-01 00:00:00
abstract::Urothelial cell carcinoma is one of the most common malignancies of the urinary tract. The standard of care, intravesical chemo- and immunotherapy, while effective, is associated with a considerable side-effect profile and approximately 30% of patients either fail to respond to treatment or suffer recurrent disease wi...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152012800617768
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND:While Thioredoxin Reductase (TrxR) plays an important role in regulation of the intracellular redox balance and various signalling pathways, Glutathione S-Transferase (GSTs) enzymes belong to the detoxification family that catalyse the conjugation of glutathione with various endogenous and xenobiotic electro...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520618666180910093335
更新日期:2018-01-01 00:00:00
abstract:AIM:This study aimed to characterize the cellular basis of the platinum cytotoxicity of two novel platinum complexes, 3Pt and 1Pt, in comparison with that of cisplatin. 3Pt comprises anionic phosphate moieties, while 1Pt comprises neutral aromatic ligands. METHODS:We compared the cytotoxic potency of 3Pt and 1Pt with ...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520615666141216151547
更新日期:2015-01-01 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) is the most frequent type of hematological cancer in the Western World. An accumulation of leukemic cells in peripheral blood of patients is a result of apoptosis disturbances as well as an increase in germinal centers CLL cell proliferation. The differences between CLL patients in t...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152010794479799
更新日期:2010-11-01 00:00:00
abstract::Of late medicinal plants and functional foods rich in bioactive phytochemicals have received growing attention as potential agents for cancer chemoprevention. Accumulating evidence from epidemiological studies as well as laboratory data supports the anticancer properties of garlic widely used as a medicinal herb and s...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2008-04-01 00:00:00
abstract:BACKGROUND:Peniciketal A (Pe-A), a spiroketal compound, shows potent anticancer activities in human acute monocytic leukemia. However, the detailed mechanisms and potent targets of Pe-A remain largely unexplored. Here, we investigated the differentially expressed proteins between the Pe-A-treated group and the control ...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520619666190212124339
更新日期:2019-01-01 00:00:00
abstract::Sphingosine 1-phosphate (S1P) is a bioactive lipid with diverse biological functions, including cell proliferation, differentiation, angiogenesis, chemotaxis, and migration. Many of the activities of S1P are mediated through five closely related G-protein-coupled receptors of the sphingosine-1-phosphate receptor famil...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152011797655041
更新日期:2011-11-01 00:00:00