共查询到20条相似文献,搜索用时 31 毫秒
1.
Xiaoyan Pan Fang Wang Yanmin Zhang Hongping Gao Zhigang Hu Sicen Wang Jie Zhang 《Bioorganic & medicinal chemistry》2013,21(9):2527-2534
A novel class of Nilotinib derivatives, B1–B20, were synthesized in high yields using various substituted anilines. All the title compounds were evaluated for their inhibitory activities against Bcr–Abl and antiproliferative effects on human leukemia cell (K562). The pharmacological results indicated that some compounds exhibited promising anticancer activity. In particular, compound B14 containing tertiary amine side chain exhibited Bcr–Abl inhibitory activity similar to that of Nilotinib. It was suggested that the introduction of the tertiary amine moiety could improve Bcr–Abl inhibitory activity and antitumor effects. 相似文献
2.
《Bioorganic & medicinal chemistry letters》2014,24(12):2651-2654
In the search of new antihyperglycemic agents and following rational approach of drug designing here new 2-hydrazolyl-4-thiazolidinone-5-carboxylic acids (4a–g) with pyrazolyl pharmacophore have been synthesized via thia Michael addition reaction of 1-((3-(4-substituted phenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)thiosemicarbazides (3a–g) with maleic anhydride. The required precursors, (3a–g) were obtained by condensing known 3-(4-substituted phenyl)-1-phenyl-1H-pyrazole-4-carbaldehydes (1a–g) with thiosemicarbazide in ethanol. The newly synthesized compounds (4a–g) have been evaluated for the antihyperglycemic activity in sucrose loaded rat model and among these compounds 4d, 4f and 4g have displayed significant antihyperglycemic activity. 相似文献
3.
Gabriel Navarrete-Vazquez Paolo Paoli Ismael León-Rivera Rafael Villalobos-Molina Jose Luis Medina-Franco Rolffy Ortiz-Andrade Samuel Estrada-Soto Guido Camici Daniel Diaz-Coutiño Itzell Gallardo-Ortiz Karina Martinez-Mayorga Hermenegilda Moreno-Díaz 《Bioorganic & medicinal chemistry》2009,17(9):3332-3341
The 2-arylsulfonylaminobenzothiazole derivatives 1–27 were prepared using a one step reaction. The in vitro inhibitory activity of the compounds against protein tyrosine phosphatase 1B (PTP-1B) was evaluated. Compounds 4 and 16 are rapid reversible (mixed-type) inhibitors of PTP-1B with IC50 values in the low micromolar range. The most active compounds (4 and 16) were docked into the crystal structure of PTP-1B. Docking results indicate potential hydrogen bond interactions between the nitro group in both compounds and the catalytic amino acid residues Arg 221 and Ser 216. Both compounds were evaluated for their in vivo antihyperglycemic activity in a type 2 diabetes mellitus rat model, showing significant lowering of plasma glucose concentration, during the 7 h post-intragastric administration. 相似文献
4.
Fateh V. Singh Amrita Parihar Sumit Chaurasia Amar B. Singh Salil P. Singh Akhilesh K. Tamrakar Arvind K. Srivastava Atul Goel 《Bioorganic & medicinal chemistry letters》2009,19(8):2158-2161
Various functionalized mono- and diarylanthranilo-1,3-dinitriles were synthesized and evaluated for their in vitro antihyperglycemic activity against the PTP-1B, glucose-6-phosphatase, glycogen phosphorylase and α-glucosidase enzymes. Among various screened compounds, 5,6-diaryl substituted anthranilo-1,3-dinitriles 3a, 3b, and 3d showed good inhibitory activity against PTP-1B with IC50 values of 58–72 μM. Three of the test compounds showed significant (25–37%) lowering of plasma glucose level at 24 h in sucrose-challenged streptozotocin-induced diabetic Sprague–Dawley rat model. 相似文献
5.
Atul Kumar Ram Awatar Maurya Siddharth Sharma Pervez Ahmad A.B. Singh Gitika Bhatia Arvind K. Srivastava 《Bioorganic & medicinal chemistry letters》2009,19(22):6447-6451
A series of pyranocoumarin derivatives were synthesized and evaluated in vivo for their anti-hyperglycemic as well as anti-dyslipidemic activities. Compounds 7a, 7c, 8a, 8b, 8c, 8e and 8f have shown promising anti-hyperglycemic activities in sucrose loaded model (SLM) as well as sucrose challenged streptozotocin induced diabetic rat model (STZ). Compounds 8a and 8b were showing 38.0% and 42.0% blood glucose lowering activity in db/db mice model. In vitro anti-hyperglycemic activity evaluation exhibited that compounds 8a (IC50 = 24.5 μM) and 8b (IC50 = 36.2 μM) are potential PTP-1B inhibitors thereby revealing their possible mechanism of anti-diabetic action. Compounds 7a, 7b, 8a, 8b, 8d, 8e and 8f have shown significant anti-dyslipidemic activity in triton induced dyslipidemia in rats. 相似文献
6.
Vasudeva Rao Avupati Rajendra Prasad Yejella Annapurna Akula Girija Sankar Guntuku Bhagya Raju Doddi Venkata Rao Vutla Suvarna Ratna Anagani Lakshmana Santhi Adimulam Aruna Kumar Vyricharla 《Bioorganic & medicinal chemistry letters》2012,22(20):6442-6450
A series of some novel 2,4-thiazolidinediones (TZDs) (2a–x) have been synthesized and characterized by FTIR, 1H NMR, 13C NMR and LC mass spectral analysis. All the synthesized compounds were evaluated for their cytotoxicity, antimicrobial and in vivo antihyperglycemic activities. Among the tested compounds for cytotoxicity using Brine Shrimp Lethality assay, compound 2t ((Z)-5-(4-((E)-3-oxo-3-(thiophen-2-yl)prop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione) exhibited significant inhibitory activity at ED50 value 4.00 ± 0.25 μg/mL and this level of activity was comparable to that of the reference drug podophyllotoxin with ED50 value 3.61 ± 0.17 μg/mL. Antimicrobial activity was screened using agar well diffusion assay method against selected Gram-positive, Gram-negative and fungal strains and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. From the results of antimicrobial activity compound 2s ((Z)-5-(4-((E)-3-(3,5-bis(benzyloxy)phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione) was found to be the most active against all the tested strains of microorganisms with MIC value 16 μg/mL. In vivo antihyperglycemic effect of twenty four TZDs (2a–x) at different doses 10, 30 and 50 mg/kg b.w (oral) were assessed using percentage reduction of plasma glucose (PG) levels in streptozotocin-induced type II diabetic rat models. From the results, the novel compound 2x ((Z)-5-(4-((E)-3-(9H-fluoren-2-yl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione) exhibited considerably potent blood glucose lowering activity than that of the standard drug rosiglitazone and it could be a remarkable starting point to evaluate structure–activity relationships and to develop new lead molecules with potential cytotoxicity, antimicrobial and antihyperglycemic activities. In addition molecular docking studies were carried out against PPARγ molecular target using Molegro Virtual Docker v 4.0 to accomplish preliminary confirmation of the observed in vivo antihyperglycemic activity. 相似文献
7.
Yan-Bo Tang Dianyun Lu Zheng Chen Chun Hu Ying Yang Jin-Ying Tian Fei Ye Li Wu Zhong-Yin Zhang Zhiyan Xiao 《Bioorganic & medicinal chemistry letters》2013,23(8):2313-2318
Fifteen novel sulfathiazole-related compounds were designed as PTP1B inhibitors based on a previously reported allosteric inhibitor (1) of PTP1B. These compounds were synthesized and evaluated against human recombinant PTP1B. Six compounds (3, 4, 8 and 14–16) exhibited significant inhibitory activity against PTP1B. The most active compound (16) showed IC50 value of 3.2 μM and kinetic analysis indicated that it is a non-competitive inhibitor of PTP1B. Furthermore, compound 16 demonstrated excellent selectivity to PTP1B over other PTPs. It also displayed in vivo insulin sensitizing effect in the insulin resistant mice. 相似文献
8.
Santosh Kumar Avinash Tiwari S.N. Suryawanshi Monika Mittal Preeti Vishwakarma Suman Gupta 《Bioorganic & medicinal chemistry letters》2012,22(21):6728-6730
A new series of aryl substituted ketene dithioacetals 6a–h was synthesized and evaluated for their in vitro and in vivo antileishmanial activity against Leishmania donovani. Two compounds exhibited significant in vitro activity against intracellular amastigotes of L. donovani with IC50 values 3.56 and 5.12 μM and were found promising as compared with reference drug, miltefosine. On the basis of good Selectivity Indices (S.I.), they were further tested for their in vivo response against L. donovani/hamster model and showed significant inhibition of parasite multiplication 78% and 83%, respectively. These compounds were better than the existing antileishmanials in respect to IC50 and SI values, but were less active than miltefosine in vivo. 相似文献
9.
S.N. Suryawanshi Santosh Kumar Avinash Tiwari Rahul Shivahare Yashpal Singh Chhonker Susmita Pandey Nishi Shakya Rabi Sankar Bhatta Suman Gupta 《Bioorganic & medicinal chemistry letters》2013,23(13):3979-3982
A series of aryl S,N-ketene acetals 7(a–f) was synthesized and evaluated for their in vitro and in vivo antileishmanial activity against Leishmania donovani. All the 6 compounds exhibited significant in vitro activity against intracellular amastigotes of L. donovani with IC50 values ranging from 1.2 to 3.5 μM and were found promising as compared with reference drugs, sodium stibogluconate (SSG) and paromomycin. On the basis of good selectivity indices (SI), they were further tested for their in vivo potential against L. donovani/hamster model. Two compounds 7a and 7b showed significant inhibition of parasite multiplication, 72% and 83%, respectively. These compounds were comparable with SSG and superior to paromomycin. Preliminary in vitro metabolic investigations were also performed to assess the metabolic stability and in vitro hepatic intrinsic clearance (Clint) of compound 7b in hamster liver microsomes. 相似文献
10.
Kumar A Sharma S Gupta LP Ahmad P Srivastava SP Rahuja N Tamrakar AK Srivastava AK 《Bioorganic & medicinal chemistry》2012,20(6):2172-2179
A series of propiophenone derivatives (6-23) have been synthesized and evaluated for their in vivo antihyperglycemic activities in sucrose loaded model (SLM), sucrose challenged streptozotocin (STZ-S) induced diabetic rat model and C57BL/KsJ db/db diabetic mice model. Compound 15 and 16 were emerged as potent antihyperglycemics and lipid lowering agents. These compounds (15, 16) further validate the potency by reducing body weight and food intake in db/db mice model. Possible mechanism of action for the propiophenone derivatives was established by the evaluation in various in vitro models. Interestingly some of the compounds were efficiently inhibiting PTP-1B. 相似文献
11.
Sunny Manohar Shabana I. Khan Diwan S. Rawat 《Bioorganic & medicinal chemistry letters》2010,20(1):322-325
A series of 4-aminoquinoline–triazine conjugates with different substitution pattern have been synthesized and evaluated for their in vitro antimalarial activity against chloroquine-sensitive and resistant strains of Plasmodium falciparum. Compounds 16, 19, 28 and 35 exhibited promising antimalarial activity against both strains of P. falciparum. Cytotoxicity of these compounds was tested against three cell lines. Several compounds did not show any cytotoxicity up to a high concentration (48 μM), others exhibited mild toxicities but selective index for antimalarial activity was high for most of these conjugates. 相似文献
12.
Zhenyuan Miao Jing Zhang Liang You Juan Wang Chunquan Sheng Jiangzhong Yao Wannian Zhang Hao Feng Wei Guo Lei Zhou Wenfeng Liu Linjian Zhu Pengfei Cheng Xiaoying Che Wenya Wang Chuan Luo Yulan Xu Guoqiang Dong 《Bioorganic & medicinal chemistry》2010,18(9):3140-3146
Homocamptothecins (hCPTs) represents a new promising class of topoisomerase I inhibitors with enhanced stability and superior antitumor activity. Some phosphodiesters and phosphotriesters homocamptothecin derivatives were designed and synthesized based on our previous synthetic route. The cytotoxicity in vitro on three cancer cell lines and antitumor activity in vivo, and inhibitory properties of topoisomerase I of these derivatives were evaluated. Among them compounds 24e and 24f exhibited higher cytotoxic activity than IRT and the former exhibited the best antitumor activity in vivo and solution stability both at pH 7.4 and pH 3.0. 相似文献
13.
Eleven antidiabetic Indian medicinal plants were investigated in streptozotocin induced diabetic rat model and provided scientific validation to prove their antihyperglycemic activity. Antidiabetic principles from five plants were isolated. All the compounds isolated were evaluated for antihyperglycemic activity in streptozotocin induced diabetic rat model and activities were compared with standard drug metformin. Some compounds were also screened in db/db mice. Two compounds (PP-1 and PP-2) inhibited significantly the activity of PTPase-1B in an in vitro system. This might be the underlying mechanism of antihyperglycemic activity of these compounds. 相似文献
14.
Mahendra B. Bhalerao Sambhaji T. Dhumal Amarsinh R. Deshmukh Laxman U. Nawale Vijay Khedkar Dhiman Sarkar Ramrao A. Mane 《Bioorganic & medicinal chemistry letters》2017,27(2):288-294
New bithiazolyl hydrazones (6a–l) have been first time synthesized by carrying novel one pot cyclocondensation of 5-acyl thiazoles (1a–b), thiosemicarbazide (2) and substituted phenacyl chlorides (4a–f) in freshly prepared ionic liquid, diisopropyl ethyl ammonium acetate (DIPEAc) at room temperature. The newly synthesized compounds have been evaluated for their antitubercular activity and the compounds 3b, 6a, 6b, 6d, 6e, 6f, 6g, and 6l have displayed noticeable antitubercular activity compared to Rifampicin with tolerable cytotoxicity. All these compounds were also screened for their antibacterial activity and found that, compounds 6j and 6k have exhibited a very good antibacterial activity. Molecular docking study has shown better harmony with the evaluation trend shown by these compounds under in vitro antitubercular screening. 相似文献
15.
Guang Xian Pang Chao Niu Nuramina Mamat Haji Akber Aisa 《Bioorganic & medicinal chemistry letters》2017,27(12):2674-2677
A novel series of coumarin derivatives 6a–o, bearing isoxazole moieties were designed and synthesized. After that, they were evaluated for melanin synthesis in murine B16 cells and inhibitory effect on the growth of CA (Candida albicans), EC (Escherichia coli), SA (Staphylococcus aureus). It was found that eleven compounds (6b–f, 6j–o) showed a better activity on melanin synthesis than positive control (8-MOP). Among them, compounds 6d (242%) and 6f (390%), with nearly 1.6 and 2.6-fold potency compared with 8-MOP (149%) respectively, were recognized as the most promising candidate hits for further pharmacological study of anti-vitiligo.Seven halogen substituted compounds exhibited moderate antimicrobial activity against CA. It is interesting that 6e–f and 6l–m, which had two halogens on the benzene showed a comparable activity with Amphotericin B against CA.The evaluation of melanin synthesis in B16 cells and inhibitory effect on bacteria of above structurally diverse derivatives had also led to an outline of structure-activity relationship. 相似文献
16.
Yunjie Zhao Yongkai Cao Huizhen Chen Fei Zhuang Chao Wu Goo Yoon Weiwei Zhu Ying Su Suqing Zheng Zhiguo Liu Seung Hoon Cheon 《Bioorganic & medicinal chemistry》2019,27(6):963-977
We describe herein the design, synthesis, and biological evaluation of a series of novel protein tyrosine phosphatase 1B (PTP1B) inhibitor retrochalcones having an allyl chain at the C-5 position of their B ring. Biological screening results showed that the majority of these compounds exhibited an inhibitory activity against PTP1B. Thus, preliminary structure-activity relationship (SAR) and quantitative SAR analyses were conducted. Among the compounds, 23 was the most potent inhibitor, exhibiting the highest in vitro inhibitory activity against PTP1B with an IC50 of 0.57?µM. Moreover, it displayed a significant hepatoprotective property via activation of the IR pathway in type 2 diabetic db/db mice. In addition, the results of our docking study showed that 23, as a specific inhibitor of PTP1B, effectively transformed the WPD loop from “close” to “open” in the active site. These results may reveal suitable compounds for the development of PTP1B inhibitors. 相似文献
17.
Sharon A Pratap R Tiwari P Srivastava A Maulik PR Ram VJ 《Bioorganic & medicinal chemistry letters》2005,15(8):2115-2117
A series of 5-[(5-aryl-1H-pyrazol-3-yl)methyl]-1H-tetrazoles 3a-h have been synthesized and evaluated for their in vivo antihyperglycemic activity. Some of the synthesized compounds have shown significant glucose lowering activity in male Sprague-Dawley rats in sucrose loaded model. These compounds were also evaluated for their peroxisome proliferator activated receptor gamma agonistic property, but none of them displayed any significant activity. 相似文献
18.
Avneet Kaur Dharam P. Pathak Vidushi Sharma Sharad Wakode 《Bioorganic & medicinal chemistry》2018,26(4):891-902
A new series of substituted-N-(3,4-dimethoxyphenyl)-benzoxazole derivatives 13a–13p was synthesized and evaluated in vitro for their COX (I and II) inhibitory activity, in vivo anti-inflammatory and ulcerogenic potential. Compounds 13d, 13h, 13k, 13l and 13n exhibited significant COX-2 inhibitory activity and selectivity towards COX-2 over COX-1. These selected compounds were screened for their in vivo anti-inflammatory activity by carrageenan induced rat paw edema method. Among these compounds, 13d was the most promising analogs of the series with percent inhibition of 84.09 and IC50 value of 0.04?µM and 1.02?µM (COX-2 and COX-1) respectively. Furthermore, ulcerogenic study was performed and tested compounds (13d, 13h, 13k, 13l) demonstrated a significant gastric tolerance than ibuprofen. Molecular docking study was also performed with resolved crystal structure of COX-2 to understand the binding mechanisms of newly synthesized inhibitors in the active site of COX-2 enzyme and the results were found to be concordant with the biological evaluation studies of the compounds. These newly synthesized inhibitors also showed acceptable pharmacokinetic profile in the in silico ADME/T analyses. 相似文献
19.
《Bioorganic & medicinal chemistry letters》2020,30(17):127373
In this study, a series of compounds with 1,2,4-oxadiazole core was designed and synthesized for the optimization of JC01, an anti-inflammatory hit identified from our in-house compound library using NF-κB pathway luciferase assay and NO production assay. All the synthetic compounds 1–29 have been screened for their anti-inflammatory effects by evaluating their inhibition against LPS-induced NO release, and compound 17 exhibited the highest activity. Western blotting and immunofluorescence analysis revealed that 17 prominently inhibited LPS-induced activation of NF-κB in RAW264.7 cells and blocked the phosphorylation of p65. Consistent with these results, it was found that 17 prevented the nuclear translocation of NF-κB induced by LPS. These data highlighted 17 as a promising anti-inflammatory agent by inhibiting NF-κB activity. 相似文献
20.
Shizhen Zhao Peng Wei Mengya Wu Xiangqian Zhang Liyu Zhao Xiaolin Jiang Chenzhou Hao Xin Su Dongmei Zhao Maosheng Cheng 《Bioorganic & medicinal chemistry》2018,26(12):3242-3253
To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compound 1, a series of benzoheterocycle analogues were designed, synthesized and evaluated for their in vitro antifungal activity. The most promising compounds 13s and 14a exhibited excellent antifungal activity against C. albicans, C. neoformans, A. fumigatus and fluconazole-resistant C. albicans strains, that was superior or comparable to those of the reference drugs fluconazole and voriconazole. GC–MS analyses suggested that the novel compound 13s might have a similar mechanism to fluconazole by inhibiting fungal lanosterol 14α-demethylase (CYP51). Furthermore, compounds 13s and 14a exhibited low inhibition profiles for various human cytochrome P450 isoforms as well as excellent blood plasma stability. 相似文献