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1.
Radhe Shyam Bahare Swastika Ganguly Kiattawee Choowongkomon Supaporn Seetaha 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2015,23(1)
Background
Structural modifications of thiazolidinediones at 3rd and 5th position have exhibited significant biological activities. In view of the facts, and based on in silico studies carried out on thiazolidine-2,4-diones as HIV-1- RT inhibitors, a novel series of 2,4-thiazolidinedione analogs have been designed and synthesized.Methods
Title compounds were prepared by the reported method. Conformations of the structures were assigned on the basis of results of different spectral data. The assay of HIV-1 RT was done as reported by Silprasit et al. Antimicrobial activity was determined by two fold serial dilution method. Docking study was performed for the highest active compounds by using Glide 5.0.Results
The newly synthesized compounds were evaluated for their HIV-1 RT inhibitory activity. Among the synthesized compounds, compound 24 showed significant HIV-1 RT inhibitory activity with 73% of inhibition with an IC50 value of 1.31 μM. Compound 10 showed highest activity against all the bacterial strains.A molecular modeling study was carried out in order to investigate the possible interactions of the highest active compounds 24, 10 and 4 with the non nucleoside inhibitory binding pocket(NNIBP) of RT, active site of GlcN-6-P synthase and cytochrome P450 14-α-sterol demethylase from Candida albicans (Candida P450DM) as the target receptors respectively using the Extra Precision (XP) mode of Glide software.Conclusion
A series of novel substituted 2-(5-benzylidene-2,4-dioxothiazolidin-3-yl)-N-(phenyl)propanamides (4–31) have been synthesized and evaluated for their HIV-1 RT inhibitory activity, antibacterial and antifungal activities. Some of the compounds have shown significant activity. Molecular docking studies showed very good interaction. 相似文献2.
本文报道了2,4-二氨基-6-N1,N2-二取代肼基-喹唑啉类衍生物的合成及其抗疟活性的研究。这类化合物的合成是以2,4-二氨基6-取代苄基氨基-喹唑啉为原料经亚硝化、还原成为2,4-二氨基6-(N1-取代苄基)—肼基喹唑啉,再与相应的醛缩合而成。此类化合物经伯氏鼠疟原虫抑制性治疗初筛表明有少数具有一定的效果。有11个化合物经约氏鼠疟原虫—斯氏按蚊系统病因性初筛有效。其中化合物Ⅱ1,7,8,11,15和Ⅲ1口服2.5mg/kg,连续3天,可使受试小鼠全部得到保护。 相似文献
3.
Nikhil M. Parekh Krunal V. Juddhawala Bhaskar M. Rawal 《Medicinal chemistry research》2013,22(6):2737-2745
A new series of benzoyl chloride-substituted 2,4-thiazolidinedione derivatives have been synthesized by the condensation of 2-amino-4-aryl-thiazole and 4′-chlorosulfonyl benzylidine-2,4-thiazolidinedione. New compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. Furthermore, new products were tested for in vitro antituberculosis activity against Mycobacterium tuberculosis using isoniazid and rifampicin as control drugs. The results of bioassay demonstrated that some of the newly synthesized 2,4-thiazolidinedione derivatives emerged as lead molecules with excellent MIC (mg/mL) values against mentioned organisms compared to standard drugs. The structure of the final analogs has been confirmed on the basis of IR, 1H NMR, mass spectral, and elemental analysis. 相似文献
4.
A. Idhayadhulla R. Surendra Kumar A. Jamal Abdul Nasser S. Kavimani S. Indumathy 《Medicinal chemistry research》2012,21(11):3699-3708
A new series of compounds 3a–f were synthesized from condensation method. Newly synthesized compounds were established by IR, 1H NMR, 13C NMR, mass spectral and elemental analysis. Synthesized compounds 3a–f were screened for anticonvulsant activity. The compound 2,2′-({3-methyl-5-[2-phenylethenyl]-1H-pyrrole-2,4-diyl}dicarbonyl)dihydrazinecarbothioamide 3a showed significant activity compared with other compounds 3b–f against pentamethylene tetrazole-induced seizures. 相似文献
5.
Huo-Jian Wang Cheng-Xi Wei Xian-Qing Deng Fu-Lan Li Zhe-Shan Quan 《Archiv der Pharmazie》2009,342(11):671-675
Several 5-alkoxy-tetrazolo[1,5-a]quinazoline derivatives have been synthesized by reacting 2,4-dichloroquinazoline with various phenols or aliphatic alcohol and then with sodium azide. The structures of these compounds have been confirmed by IR, MS, 1H-NMR, and elementary analysis. Anticonvulsant activities were evaluated using the maximal electroshock (MES) test. Most of the synthesized compounds displayed weak anticonvulsant activity at a dose of 300 mg/kg. Antidepressant activities were investigated by forced swimming test. Two compounds, namely 5-(hexyloxy)tetrazolo[1,5-a]quinazoline and 5-(4-methoxyphenoxy)tetrazolo[1,5-a]quinazoline, showed significant antidepressant activity, which decreased the immobility time by 62.2 and 51.7% at 100 mg/kg dose level. 相似文献
6.
Danylo Kaminskyy Barbara Bednarczyk-Cwynar Olexandr Vasylenko Oxana Kazakova Borys Zimenkovsky Lucjusz Zaprutko Roman Lesyk 《Medicinal chemistry research》2012,21(11):3568-3580
The synthesis and evaluation of the anticancer activity of new acylated oximes derivatives of oleanolic acid with 4-thiazolidinone-3(5)-carboxylic acid moieties were described. Newly synthesized compounds were elucidated on the basis of elemental analyses and spectral data (IR, 1H, and 13C NMR). Anticancer activity of the tested compounds has been evaluated in vitro at National Cancer Institute (NCI) in which some structure activity relationships (SARs) were discussed. Among the tested compounds, 3-[(2,4-thiazolidinedione-5-ylidene)-carboxyimino]olean-12-en-28-oic acid methyl ester (IVm) was superior to other related compounds with mean values of pGI50?=?5.51/5.57, pTGI?=?5.09/5.13, and pLC50?=?4.62/4.64, low toxicity and moderate activity level in vivo hollow fiber assay. 相似文献
7.
Shankar G. Alegaon Kallanagouda R. Alagawadi Sneha M. Pawar D. Vinod Udaysingh Rajput 《Medicinal chemistry research》2014,23(2):987-994
As a part of our continuation studies in developing new derivatives as dual antimicrobial/antitumor agents we describe the synthesis of new (Z)-2-(5-arylidene-2,4-dioxothiazolidin-3-yl) acetic acid derivatives (3a–m). The chemical structures of the compound were elucidated by FTIR, 1H NMR, 13C NMR, and elemental analysis data. The antimicrobial activity of all products was examined. All newly synthesized compounds were tested for their in vitro anticancer activity against four cancer cell lines. Among the synthesized compounds, 3a exhibited notable activity against HeLa, HT29, A549, and MCF-7 cell lines with IC50 values of 55, 40, 38, and 50 μM, respectively. In order to predict the drug likeliness of the synthesized compounds on the guidelines of Lipinski rule of five studies was carried out using Pallas software. 相似文献
8.
E. N. Al-kaissi N. F. Al-Ghrary N. K. Al-Kaisi A. Al-Shamma Z. Muhi-eldeen 《Medicinal chemistry research》2012,21(11):3390-3395
A series of 4,5-diaryl-2-[4-(t-amino)-2-butynyl]-2,4-dihydro-3H-1,2,4-triazol-3-ones were synthesized and characterized by infrared spectrum (IR), 1H-NMR spectra and elemental analyses. Investigation of their antimicrobial activity was performed. Antimicrobial activity profile of the title compounds were evaluated against Gram- positive bacteria, Gram-negative bacteria and fungi. The synthesized compounds displayed different degrees of antimicrobial activities as shown in Table?3. Compound 12 was the most active one. This may be attributed to 4,5-diphenylsubstituent on the triazoline-3-one ring and the nature of the amino groups at terminal acetylenic moiety. 相似文献
9.
Yuriy M. Kononevich Ludmila S. Bobkova Alexander S. Smolski Anatoly M. Demchenko 《Scientia pharmaceutica》2015,83(1):41-48
New 7-thio derivatives of 6,7-dihydro-1H-cyclopenta[d]pyrimidine-2,4(3H,5H)-dione have been synthesized by the reaction of 3-cyclohexyl-7-thio-6,7-dihydro-1H-cyclopenta[d]pyrimidine-2,4(3H,5H)-dione with alkylhalogenides. The synthesized compounds were tested for antioxidant activity on the model of Fe2+-dependent oxidation of adrenaline in vitro. It was found that the antiradical activity of 7-thio derivatives of 6,7-dihydro-1H-cyclopenta[d]pyrimidine-2,4(3H,5H)-dione significantly depends on the structure of the substituent which is part of the thioether fragment of the base molecule. 相似文献
10.
Cristina Nastasă Brînduşa Tiperciuc Alina Pârvu Mihaela Duma Ioana Ionuţ Ovidiu Oniga 《Archiv der Pharmazie》2013,346(6):481-490
A novel series of 5‐arylidene ‐ 2,4‐thiazolidinediones (TZDs) 2a – p was synthesized from the condensation of 3‐((2‐phenylthiazol‐4‐yl)methyl)thiazolidine‐2,4‐dione with different benzaldehyde derivatives. All the structures were confirmed by their spectral (IR, 1H NMR, 13C NMR and mass) and elemental analytical data. The new molecules were evaluated in vivo as anti‐inflammatory agents in an acute experimental inflammation, evaluating the acute phase bone marrow response and phagocyte activity. All compounds, excepting one, reduced the absolute leukocytes count due to the lower neutrophil percentage. Phagocytary index was decreased by the same molecules, while only half of them reduced the phagocytary activity. The effect was superior to meloxicam, the reference anti‐inflammatory drug, for the majority of the TZD derivatives. The new molecules were also investigated for their antimicrobial properties on Gram‐positive and Gram‐negative bacteria and one fungal strain. Two compounds ( 2e and 2n ) manifested growth inhibition capacity on all the tested strains. 相似文献
11.
Abdul Rauf Sumaira Liaqat Ashfaq M. Qureshi Muhammad Yaqub Aziz U. Rehman Mahmood U. Hassan Zahid H. Chohan Faiz U. H. Nasim T. Ben Hadda 《Medicinal chemistry research》2012,21(1):60-74
Abstract
5-Substituted-8-methyl-2H-pyrido[1,2-a]pyrimidine-2,4(3H)-dione and its anilines, amino pyridines and hydrazides derivatives were prepared in a good to excellent yields. In the first step 8-methyl-2H-pyrido[1,2-a]pyrimidine-2,4(3H)-dione (1) was prepared by reacting 4-methyl-2-aminopyridine, with diethylmalonate. Compounds substituted pyrido[1,2-a]pyrimidine-2,4(3H)-diones (PPMDO) (2)–(17) were prepared by condensing 8-methyl-2H-pyrido[1,2-a]pyrimidine-2,4(3H)-dione in the presence of triethylorthoformte (TEF) and dimethylformamide (DMF), with respective amino components viz. 2-aminoacetophenone, 3-aminoacetophenone, 4-aminoacetophenone, 2,4,6-trimethylaniline, 2-fluoroaniline, 3-fluoroaniline, 4-fluoroaniline, 2-aminothiophenol, 2-amino-4-methylpyridine, 2-amino-5-methylpyridine, 2-amino-5-nitropyridine, Benzoic hydrazide, 4-nitrobenzoic hydrazide, 4-bromobenzoic hydrazide, 4-chlorobenzoic hydrazide and 4-hydroxybenzoic hydrazide, respectively. The chemical structures of all the compounds were elucidated by IR, 1H-NMR, 13C-NMR and elemental analysis data. The synthesized compounds were screened for their in vitro urease inhibition activity, by the phenol hypochlorite method. These compounds were found to exhibit either no or low to moderate or significant activity. The compounds (9) and (14) showed comparatively much higher activity. However, the compound (9) was found to be the most active one. 相似文献12.
Nazar Trotsko Urszula Kosikowska Agata Paneth Monika Wujec Anna Malm 《Saudi Pharmaceutical Journal》2018,26(4):568-577
A series of new (2,4-dioxothiazolidin-5-yl/ylidene)acetic acid derivatives with thiazolidine-2,4-dione, rhodanine and 2-thiohydantoin moiety (28–65) were synthesized by the reaction of (2,4-dioxothiazolidin-5-yl/ylidene)acetic acid chlorides with 5-(hydroxybenzylidene) thiazolidine-2,4-dione, rhodanine and 2-thiohydantoin derivatives. Obtained compounds (28–65) were tested on reference strains of Gram-positive bacteria and ones of the Gram-negative bacteria. The antibacterial activity of target compounds was determined by broth microdilution method. These derivatives showed antibacterial activity generally against Gram-positive bacterial strains. Most active compounds possess MIC?=?3.91?mg/L. Our results suggest that presence of electron-withdrawing substituent at phenyl ring is favorable while geometry of molecule does not play important role in antibacterial response. It was confirmed the lack of direct influence of substitution pattern at phenyl ring on antibacterial activity of closely related compounds of series 1–3. The antibacterial activity of some compounds was similar or higher than the activity of commonly used reference drugs such as oxacillin and cefuroxime. 相似文献
13.
A series of pyridine derivatives of thiazolidin-4-ones (4a–4o) has been synthesized. Structures of these compounds were established on the basis of elemental analysis, IR, 1H NMR, 13C NMR, and Mass spectral data. All the synthesized compounds have been evaluated for their anti-inflammatory and analgesic effects. The results showed that compound 2-[4-methylphenylimino]-5-(1H-pyridin-2-ylmethylidene)-1,3-thiazolidin-4-one (4d), 2-(2,4-dinitro-phenylhydrazinylidine)-5-(1H-pyridin-2-yl-methylidene)-1,3-thiazolidin-4-one (4h), and 2-[3-nitro-phenylimino]-5-(1H-pyridin-2-yl-methylidene)-1,3-thiazolidin-4-one (4j) exhibited good anti-inflammatory and analgesic activity. Compound 4h was found to be the most active compound of the series with an interesting dual anti-inflammatory and analgesic activity. Docking simulation was performed to position synthesized compounds into the active site of COX-2. The relationships of energy-based docking score with analgesic and anti-inflammatory activities were also investigated by linear regression method. The QSAR models with R 2 of 0.621 and 0.740 were developed for analgesic and anti-inflammatory activities, respectively. 相似文献
14.
RYSZARD ANDRUSZKIEWICZ HENRYK CHMARA SLAWOMIR MILEWSKI EDWARD BOROWSKI 《Chemical biology & drug design》1986,27(5):449-453
Several analogues of N3-fumaramoyl-L-2,3-diaminopropanoic acid were synthesized and evaluated for inhibition of glucosamine-6-phosphate synthetase activity. The syntheses were accomplished by acylation reaction of N2-tert.-butoxycarbonyl-L-2,3-diaminopropanoic acid (Boc-A2pr) or N2-tert.-butoxy-carbonyl-L-2,4-diaminobutanoic acid (Boc-A2-bu) with the N-succinimidoyl esters of several derivatives of α, β-unsaturated acids 2a-d followed by deprotection of the Boc groups. The obtained compounds were tested for inhibition of glucosamine synthetase isolated from Salmonella typhimurium and Saccharomyces cerevisiae. The results indicated that among the synthesized compounds, N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic acid (FMDP) was the most powerful inhibitor of glucosamine synthetase. 相似文献
15.
Jeong In Yun Eun Hye Yang Muhammad Latif Hyeon Ji Lee Kwangho Lee Chang-Soo Yun Chi Hoon Park Chong Ock Lee Chong Hak Chae Sung Yun Cho Hee Jung Jung Pilho Kim Sang Un Choi Hyoung Rae Kim 《Archives of pharmacal research》2014,37(7):873-881
A new series of 2,4-dianilino-5-fluoropyrimidine derivatives were designed and synthesized and their anaplastic lymphoma kinase (ALK) inhibitory activities were evaluated by biochemical and cell-based assays in order to discover a new ALK inhibitor. Most compounds synthesized showed good inhibitory activities against ALK and good cytotoxic activities in H3122 cell line. The best compound 6f showed good activity against wild-type ALK along with crizotinib-resistant mutant ALK, and it showed 6 times better activity in cell-based assay than crizotinib. Some SAR studies were performed by the comparisons of the activities between 6 and the designed-synthesized compounds. 相似文献
16.
Rahul P. Modh Amit C. Patel Dharmesh H. Mahajan Christophe Pannecouque Erik De Clercq Kishor H. Chikhalia 《Archiv der Pharmazie》2012,345(12):964-972
In an attempt to afford possible antibacterial and anti‐human immunodeficiency virus (HIV) agents, a series of 22 novel styryl quinazoline‐based heterocyclic entities were designed and synthesized. Various substituted aryl urea and thiourea cores were incorporated at position 4 of quinazoline, followed by styrylation of position 2, aiming at an augmented biological potential. The synthesized compounds were well characterized through IR, 1H NMR, 13C NMR and elemental analyses. All compounds were screened for their in vitro anti‐HIV activity against the HIV‐1 (IIIB) and HIV‐2 (ROD) strains. The antibacterial activity was also evaluated against various pathogenic Gram‐positive and Gram‐negative bacterial strains. 相似文献
17.
New (Z)-5-substituted-2,4-thiazolidinediones (3a–m) were easily prepared by the condensation of thiazolidine-2,4-dione (1) with suitable aldehydes (2a–m) via microwave irradiation technique. The reaction between (Z)-5-substituted-2,4-thiazolidinediones and 4-(bromomethyl) benzoic acid, using potassium carbonate as base in refluxing acetone, followed by a workup in acidic medium provided 4-(((Z)-5-substituted-2,4-dioxothiazolidin-3-yl)methyl) benzoic acid derivatives (4a–m). The structures of the newly synthesized compounds were confirmed by IR, 1H NMR, 13C NMR spectral studies, and elemental analysis. All compounds were evaluated for their in vitro antimicrobial and cytotoxic activities. Antibacterial and antifungal results revealed that most of the compounds showed significant activity where as compounds 4c and 4g are found to be broad spectrum antibacterial and antifungal properties, the MIC values were observed in the range of 2–4 and 2–8?μg/ml, respectively. In MTT cytotoxicity studies, the compound 4g was found most potent. In HeLa, HT29, A549, and MCF-7 cells, the IC50 values were observed in the range of 30–36?μM. 相似文献
18.
Wenya Wang Chunquan Sheng Xiaoying Che Haitao Ji Zhenyuan Miao Jianzhong Yao Wannian Zhang 《Archiv der Pharmazie》2009,342(12):732-739
A series of new triazole derivatives were designed and synthesized on the basis of the active site of lanosterol 14α‐demethylase from Candida albicans (CACYP51). 2‐(2,4‐Difluorophenyl)‐3‐(methyl‐(3‐phenoxyalkyl)amino)‐1‐(1H‐1,2,4‐triazol‐1‐yl)propan‐2‐ols show excellent in‐vitro activity against most of the tested pathogenic fungi. The MIC80 value of compound 8a against Candida albicans is 0.01 μM, which provides a good starting template for further structural optimization. The binding modes of the designed compounds were investigated by flexible molecular docking. The compounds interacted with CACYP51 through hydrophobic, van‐der‐Waals, and hydrogen‐bonding interactions. 相似文献
19.
目的以IMC-038525为先导化合物,设计并合成4-苯基-1,3,5-三嗪-2-胺类化合物,考察其体外抗肿瘤活性。方法以2,4-二氯-1,3,5-三嗪为起始原料,经过氨化、Suzuki偶联和还原胺化合成一类4-苯基-1,3,5-三嗪-2-胺类化合物,采用噻唑蓝法(MTT)测定其对肿瘤细胞的抑制活性。结果设计并合成了13个新化合物,结构经1H-NMR和MS确证。活性测试结果显示该类化合物具有一定的抗肿瘤活性。结论合成了一类4-苯基-1,3,5-三嗪-2-胺类衍生物,具有一定抑瘤活性的化合物,为新型抗肿瘤化合物的设计与合成提供思路。 相似文献
20.
Mehtab Parveen Akhtar Ali Mahboob Alam Asad U. Khan Anis Ahmad 《Medicinal chemistry research》2013,22(7):3085-3095
A series of novel oxadiazinan-5-one namely 2-methyl-2-phenyl-1,3,4-oxadiazinan-5-one (6), 2-(3-hydroxyphenyl)-2-methyl-1,3,4-oxadiazinan-5-one (7), 2-(4-hydroxyphenyl)-2-methyl-1,3,4-oxadiazinan-5-one (8), 2-(2,4-dihydroxyphenyl)-2-methyl-1,3,4-oxadiazinan-5-one (9) and 2-(2,5-dihydroxyphenyl)-2-methyl-1,3,4-oxadiazinan-5-one (10) have been synthesized by the reaction of acetophenone and its derivatives with cyanoacetic acid hydrazide. The structural assignments of the products were done on the basis of IR, 1H NMR, 13C NMR, MS, and analytical data. The in vitro antioxidant and antimicrobial activity of all the synthesized compounds (6–10) was tested by the DPPH and disk diffusion method, respectively. The synthesized compounds were screened against Gram-positive and Gram-negative bacterial and fungal strains. Compound (7) showed the highest inhibition comparable with the standard antibiotic drugs Ciprofloxacin and Amphotericin B. The antibacterial activity of the synthesized compounds was further investigated with the help of in silico docking study using Discovery studio 3.1, Molego Virtual Docker and LigandScout to predict the active sites. 相似文献