925005-67-0Relevant articles and documents
Design, synthesis and antitubercular activity of certain nicotinic acid hydrazides
Eldehna, Wagdy M.,Fares, Mohamed,Abdel-Aziz, Marwa M,Abdel-Aziz, Hatem A
, p. 8800 - 8815 (2015)
Three series of 6-Aryl-2-methylnicotinohydrazides 4a-i, N'-Arylidene-6-(4-bromophenyl)-2-methylnicotino hydrazides 7a-f, and N'-(un/substituted 2-oxoindolin-3-ylidene)-6-(4-fluorophenyl)-2-methylnicotinohydrazides 8a-c were synthesized and evaluated for their potential in vitro antimycobacterial activity against M.Tuberculosis. The results showed that isatin hydrazides 8a-c are remarkably more active than the parent hydrazide 4c. Hydrazides 8b and 8c exhibited the highest activity among all the tested compounds (MIC = 12.5 and 6.25 μg/mL, respectively). Compounds 8b and 8c were also devoid of apparent cytotoxicity to HT-29, PC-3, A549, HepG2 and MCF-7 cancer cell lines. Besides, 8b and 8c showed good drug-likeness scores of 0.62 and 0.41, respectively. Those two isatin hydrazides could offer an excellent framework for future development to obtain more potent antitubercular agents. The SAR study suggested that lipophilicity of the synthesized derivatives is a crucial element that accounts for their antimycobacterial activity. Finally, a theoretical kinetic study was established to predict the ADME of the active derivatives.
Synthesis and in vitro anticancer activity of certain novel 1-(2-methyl-6-arylpyridin-3-yl)-3-phenylureas as apoptosis-inducing agents
Eldehna, Wagdy M.,Hassan, Ghada S.,Al-Rashood, Sara T.,Alkahtani, Hamad M.,Almehizia, Abdulrahman A.,Al-Warhi, Tarfah,Altyar, Ahmed E.,Abdel-Aziz, Hatem A.
, p. 322 - 332 (2019)
In connection with our research program on the development of novel anticancer candidates, herein we report the design and synthesis of novel series of 1-(2-methyl-6-arylpyridin-3-yl)-3-phenylureas 5a–l. The target pyridins were evaluated for their in vitro anticancer activity against two cancer cell lines: non-small cell lung cancer A549 cell line and colon cancer HCT-116 cell line. Compound 5l emerged as the most active congener towards both A549 and HCT-116 cell lines with IC50 values equal to 3.22 ± 0.2 and 2.71 ± 0.16 μM, respectively, which are comparable to those of Doxorubicin; 2.93 ± 0.28 and 3.10 ± 0.22, respectively. Furthermore, compound 5l stood out as the most potent pyridine derivative (mean % GI = 40), at US-NCI Developmental Therapeutic Program anticancer assay, with broad-spectrum antitumor activity against the most tested cancer cell lines from all subpanels. Compound 5l was able to provoke apoptosis in HCT-116 cells as evidenced by the decreased expression of the anti-apoptotic Bcl-2 protein, and the enhanced expression of the pro-apoptotic proteins levels; Bax, cytochrome C, p53, caspase-3 and caspase-9. Moreover, 5l disrupted the HCT-116 cell cycle via alteration of the Sub-G1 phase and arresting the G2-M stage. Also, 5l showed a significant increase in the percent of annexinV-FITC positive apoptotic cells from 1.99 to 15.76%.
Novel arylpyridine-based 1,3,4-oxadiazoles: Synthesis, antibacterial, and anti-inflammatory evaluation
Padejjar Vasantha, Sowmya,Poojary, Boja,Bistuvalli Chandrashekarappa, Revanasiddappa
, p. 638 - 650 (2019/05/15)
In view of developing novel bioactive compounds, a series of 2-(5-[2-methyl-6-arylpyridin-3-yl]-1,3,4-oxadiazol-2-ylthio)-1-arylethanones (6a–n) were designed and synthesized in good yield. Novel compounds were evaluated for their antibacterial and anti-i
Design, synthesis and 2D QSAR study of novel pyridine and quinolone hydrazone derivatives as potential antimicrobial and antitubercular agents
Abdelrahman, Mohamed A.,Salama, Ismail,Gomaa, Mohamed S.,Elaasser, Mahmoud M.,Abdel-Aziz, Marwa M.,Soliman, Dalia H.
, p. 698 - 714 (2017/07/18)
The increased development of highly resistant bacterial strains and tuberculosis, constitute a serious public health threat, highlighting the urgent need of novel antibacterial agents. In this work, two novel series of nicotinic acid hydrazone derivatives (6a-r) and quinolone hydrazide derivatives (12a-l) were synthesized and evaluated as antimicrobial and antitubercular agents. The synthesized compounds were evaluated in vitro for their antibacterial, antifungal and antimycobacterial activities. Compounds 6f and 6p bearing the 3,4,5- (OCH3)3 and 2,5-(OCH3)2 benzylidene motifs were the most potent and as antibacterial, antifungal (MIC: 0.49–1.95 μg/mL) and (MIC: 0.49–0.98 μg/mL) respectively and antimycobacterial activity (MIC = 0.76 and 0.39 μg/mL) respectively. Besides, several derivatives, 6e, 6h, 6l-6o, 6q, 6r, 12a, 12b, 12e, 12h, 12k and 12l, exhibited significant antibacterial and antifungal activities with MIC values ranging from 1.95 to 7.81 μg/mL, they also displayed excellent to good activity against Mycobacterium tuberculosis with MIC range from 0.39 to 3.12 μg/mL. In addition, some of the most active compounds were tested for cytotoxic activities against human lung fibroblast normal cells (WI-38) and displayed low toxicity. Moreover, 2D-QSAR models to characterize the descriptors controlling the observed activities, were generated and validated.
Protective effect of novel substituted nicotine hydrazide analogues against hypoxic brain injury in neonatal rats via inhibition of caspase
Deng, Chang-Bo,Li, Juan,Li, Lu-Yi,Sun, Feng-Jie
supporting information, p. 3195 - 3201 (2016/06/13)
In hypoxic-ischemic injury of the brain of neonates, the level of caspase-3 was found to be aberrantly activated. Its overexpression leads to the alteration of cytoskeleton protein fodrin and loss of DNA repair enzyme which ultimately results in neurological impairment and disability. Concerning this, the present study was intended to develop novel nicotine hydrazide analogues as caspase inhibitors via efficient synthetic route. These compounds were subsequently tested for inhibitory activity against caspase-3 and -7 where they exhibit highly potent activity against caspase-3 revealing compound 5k as most potent inhibitor (IC50 = 19.4 ± 2.5 μM). In Western blot analysis, 5k considerably inhibits the overexpression of caspase-3. The aryl nicotinate of compound 5k, as indicated by molecular docking was found to engage His121 and critical enzyme thiols, i.e., Cys163 of caspase-3 for its potent activity. Moreover, histopathological examination of brain tissues and hippocampus neurons showed that compound 5k considerably improves the brain injury and exert neuroprotective effects in hypoxic-ischemic (HI). In brain homogenate, 5k significantly improves the activity of MDA, SOD, GSH-Px, CAT and T-AOC to exert its beneficial effect against oxidative stress induced by HI injury.
Design, synthesis and QSAR study of certain isatin-pyridine hybrids as potential anti-proliferative agents
Eldehna, Wagdy M.,Altoukhy, Ayman,Mahrous, Hoda,Abdel-Aziz, Hatem A.
, p. 684 - 694 (2015/02/02)
A hybrid pharmacophore approach was adopted to design and synthesize new series of isatin-pyridine hybrids. All the newly prepared hybrids (5a-o, 8 and 11a-d) were in vitro evaluated for their anti-proliferative activity against three human cancer cell lines, namely HepG2 hepatocellular carcinoma, A549 lung cancer and MCF-7 breast cancer. Compound 8 emerged as the most active member against HepG2 cell line (ICinf50/inf = 2.5 ± 0.39 μM), with 2.7-fold increased activity than the reference drug, doxorubicin (ICinf50/inf = 6.9 ± 2.05 μM). Whilst, compound 11c was found to be the most potent counterpart against A549 and MCF-7 cell lines with ICinf50/inf values of 10.8 ± 1.15 and 6.3 ± 0.79, respectively. The weightiness of the utilization of non-cleavable linker, as the chalcone linker, and simplification of the first group, was explored via the SAR study. Furthermore, a QSAR model was built to explore the structural requirements controlling the cytotoxic activities. Notably, the predicted activities by the QSAR model were very close to those experimentally observed, hinting that this model could be safely applied for prediction of more efficacious hits comprising the same skeletal framework. Finally, a theoretical kinetic study was established to predict the ADME of the active hybrids.
Design, synthesis and pharmacophoric model building of novel substituted nicotinic acid hydrazones with potential antiproliferative activity
Abdel-Aziz, Hatem A.,Aboul-Fadl, Tarek,Al-Obaid, Abdul-Rahman M.,Ghazzali, Mohamed,Al-Dhfyan, Abdullah,Contini, Alessandro
, p. 1543 - 1552 (2013/03/13)
Novel 6-aryl-2-methylnicotinic acid hydrazides 4a-c and their corresponding hydrazones 5a-c and 6a-i were synthesized. X-ray single crystal diffraction of 6h confirmed the chemical structure of hydrazones 6a-i. Antiproliferative activity of the synthetic compounds was investigated against K562 leukemia cell lines. Variable cell growth inhibitory activities were obtained with IC 50 range from 24.99 to 66.78 μM where the compound 6c exhibited the maximum activity. Structure activity relationship analysis has been performed and a common pharmacophore model for the synthesized derivatives has been obtained by using the pharmacophore elucidation module of the software MOE. The best model obtained is characterized by two projected locations of potential H-bond donors (F3 and F4) and two Aromatic annotations (F1 and F2).
