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1.
Omega-(2-Naphthyloxy) amino alkanes as a novel class of anti-hyperglycemic and lipid lowering agents
omega-(2-Naphthyloxy) amino alkanes, obtained as major by-product during course of synthesis of carbamate esters from omega-(2-naphthyloxy) alkyl halides and amines, showed significant anti-hyperglycemic and lipid lowering activities in various test models as a novel class of compounds. Compounds were tested in rat GLM, SLM, STZ, and STZ-S models at 100mg/kg dose. Of these compound 13 was found to be the most active which caused lowering of sugar by 33.6%, 31.0%, 28.5%, and 73.8% in GLM, SLM, STZ, STZ-S, and db/db mice models, respectively. It also significantly effected lowering of LDL in rat model and also in Hamster model without reducing HDL. Most of the compounds showing anti-diabetic and lipid lowering activity have shown promising PPAR-alpha/gamma/delta-activity. Compounds 6, 13, and 19 have shown very good PPAR-alpha/gamma/delta activity. 相似文献
2.
Atul Kumar Siddharth Sharma Vishwa Deepak Tripathi Ram Awatar Maurya Swayam Prakash Srivastava Gitika Bhatia A.K. Tamrakar Arvind Kumar Srivastava 《Bioorganic & medicinal chemistry》2010,18(11):4138-4148
A series of 2,4-disubstituted polyhydroquinoline were synthesized and evaluated for their in vivo antihyperglycemic as well as antidyslipidemic activities. Several synthesized compounds have exhibited promising in vivo antihyperglycemic in SLM, STZ-S, and db/db mice model along with significant lipid and TG modulating activity. All these compounds were evaluated in various in vitro models of diabetes to know the possible mechanism of their antihyperglycemic action. Interestingly, compounds 3a–r (diaryl substitution) have exhibited promising protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity whereas, compounds 5a–d (acid substituted) have shown significant glycogen phosphorylase activity. 相似文献
3.
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
4.
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
5.
Singh FV Chaurasia S Joshi MD Srivastava AK Goel A 《Bioorganic & medicinal chemistry letters》2007,17(9):2425-2429
Various nature-mimicking pyranones such as 6-(2,5-dimethylfuran-3-yl)-pyran-2-one and 6-(furan-2-yl)-pyran-2-one derivatives were synthesized and evaluated for their in vivo antihyperglycemic activity in sucrose-loaded streptozotocin-induced diabetic rat model. Five of the test compounds showed significant lowering of plasma glucose level in STZ-S model. 相似文献
6.
Samar Said Fatahala Shahenda Mahgub Heba Taha Rania Helmy Abd-El Hameed 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):809-817
Pyrrolopyrimidin-4-ylidene-malononitriles IIa–d were prepared as important intermediates for preparation of a new series of spiro-pyrrolopyrimidines. These intermediates undergo cyclisation via reaction with acetylacetone, guanidine hydrochloride or hydrazine hydrate. Elemental and spectroscopic evidences for the structures of these compounds are presented. The final compounds have been monitored for in vivo anti-hyperglycemic activity, compared with Amaryl as standard drug. Among 12 tested compounds, both spiro (pyrano IIIb and pyrazlo Va) derivatives exhibit promising anti-hyperglycemic activity. 相似文献
7.
Satyanarayana M Tiwari P Tripathi BK Srivastava AK Pratap R 《Bioorganic & medicinal chemistry》2004,12(5):883-889
A series of aryloxypropanolamines (5a-r) of different chalcones (3a-e) were synthesized and evaluated for antihyperglycemic activity in sucrose loaded (SLM) and streptozotocin (STZ) induced diabetic animal models. Among them compounds 5a, g, m, o, p and r showed significant reduction in blood glucose levels in both SLM and STZ animal models. 相似文献
8.
Shukla P Singh AB Srivastava AK Pratap R 《Bioorganic & medicinal chemistry letters》2007,17(3):799-802
A series of chalcone based aryloxypropanolamines were synthesized and evaluated for their antihyperglycemic activity in SLM and STZ rat models. Most of the compounds exhibited moderate to good activity ranging from 6.5% to 31.1% in SLM and 8.3% to 22.6% in STZ models, respectively. The most potent compound 5 g exhibited glucose lowering of 26.7% in SLM and 22.6% in STZ models. A definite structure-activity relationship was observed while varying the nature as well as the position of the amine in ring B. 相似文献
9.
Ning Li Li-Jun Wang Bo Jiang Shu-Ju Guo Xiang-Qian Li Xue-Chun Chen Jiao Luo Chao Li Yi Wang Da-Yong Shi 《Bioorganic & medicinal chemistry letters》2018,28(12):2131-2135
A series of novel pyrimidinedione derivatives were designed and evaluated for in vitro dipeptidyl peptidase-4 (DPP-4) inhibitory activity and in vivo anti-hyperglycemic efficacy. Among them, the representative compounds 11, 15 and 16 showed excellent inhibitory activity of DPP-4 with IC50 values of 64.47?nM, 188.7?nM and 65.36?nM, respectively. Further studies revealed that compound 11 was potent in vivo hypoglycemic effect. The structure–activity relationships of these pyrimidinedione derivatives had been discussed, which would be useful for developing novel DPP-4 inhibitors as treating type 2 diabetes. 相似文献
10.
11.
Dwivedi AP Kumar S Varshney V Singh AB Srivastava AK Sahu DP 《Bioorganic & medicinal chemistry letters》2008,18(7):2301-2305
A series of novel N-acyl-2-arylethylamines and N-acyl-3-coumarylamines were synthesized and evaluated for their antihyperglycemic activity. Compounds 3g and 6d exhibited lowering of postprandial plasma glucose by 30.7%, 23.3% in SLM and 25.6%, 25.4% in STZ models respectively which is significant compared to metformin and glybenclamide. Other compounds exhibited moderate to good activity ranging from 19.5% to 32.8% in SLM and 3.26% to 25.4% in STZ models. 相似文献
12.
Goel A Agarwal N Singh FV Sharon A Tiwari P Dixit M Pratap R Srivastava AK Maulik PR Ram VJ 《Bioorganic & medicinal chemistry letters》2004,14(5):1089-1092
Various 3,4,5-triarylpyrroles were synthesized and evaluated for their in vivo antihyperglycemic activity in sucrose-loaded (SLM) and/or streptozotocin-induced (STZ) diabetic rat models. Three of the test compounds, 2-methyl-4,5-diphenyl-3-substituted-phenyl-1H-pyrroles (3c, d and h) showed significant inhibition on postprandial hyperglycemia in normal rats post sucrose loaded. These compounds also showed lowering of plasma glucose level in STZ-induced diabetic rat model. 相似文献
13.
Khaled M. Darwish Ismail Salama Samia Mostafa Mohamed S. Gomaa El-Sayed Khafagy Mohamed A. Helal 《Bioorganic & medicinal chemistry letters》2018,28(9):1595-1602
Type-2 diabetes mellitus is a progressive cluster of metabolic disorders, representing a global public health burden affecting more than 366?million people worldwide. We recently reported the discovery of three series of novel agents showing balanced activity on two metabolic receptors, peroxisome proliferator activated receptor-γ (PPAR-γ) and free fatty acid receptor 1 (FFAR1), also known as GPCR40. Our designing strategy relied on linking the thiazolidinedione head with known GPCR privilege structures. To further investigate this concept, two new scaffolds, the benzhydrol- and indole-based chemotypes, were introduced here in. Our optimization campaign resulted in three compounds; 15a, 15c, and 15d, with affinities in the low micromolar range on both targets. In vivo study of selected test compounds, revealed that 15c possesses a significant anti-hyperglycemic and anti-hyperlipidemic activities superior to rosiglitazone in fat-fed animal models. Molecular docking analysis was conducted to explain the binding modes of both series. These compounds could lead to the development of the unique antidiabetic agent acting as insulin sensitizer as well as insulin secretagogue. 相似文献
14.
Baoshun Zhang Tingting Chen Zhu Chen Mingxue Wang Dengyu Zheng Jinfeng Wu Xiaofei Jiang Xuegang Li 《Bioorganic & medicinal chemistry letters》2012,22(23):7194-7197
A series of hesperidin derivatives were prepared and identified by IR, 1H NMR, and MS spectra. These compounds were evaluated in vitro and in vivo based on α-glucosidase inhibition, glucose consumption of HepG2 cells, and blood glucose level in streptozotocin-induced diabetic mice. The results revealed that all the compounds exhibited anti-hyperglycemic activities. The inhibition at 10?3 M of compounds 3 and 7a on α-glucosidase were 55.02% and 53.34%, respectively, as compared to 54.80% by acarbose. Treated by compound 3 and the reference drug metformin, glucose consumption of HepG2 cell were 1.78 and 2.11 mM, respectively. After the streptozotocin-induced diabetic mice were oral administrated with compound 3 at 100 mg kg?1 d?1 for 10 days, the blood glucose level of 3 treated mice (13.23 mM, P <0.05) showed significant difference when compared to model control (23.03 mM). Thus, compound 3 exhibited promising anti-hyperglycemic activity. 相似文献
15.
Chen XB Zhuang JJ Liu JH Lei M Ma L Chen J Shen X Hu LH 《Bioorganic & medicinal chemistry》2011,19(19):5776-5781
AMP-activated kinase (AMPK) as a key controller in the regulation of whole-body energy homeostasis, plays an important role in protecting the body from metabolic diseases. Recently, improved glucose, lipid utility and increased insulin sensitivity were observed on several diabetic rodent models treated with crude mogrosides isolated from the fruit of Siraitia grosvenorii Swingle, but the precise active compounds responsible for the anti-diabetic activity of this plant have not been clearly identified. In our current work, acid hydrolysis of crude mogrosides provided five new cucurbitane triterpenoids (1-4, 8), along with three known ones (5-7). The main aglycone mogrol (7) and compounds 4 and 8 were found to be potent AMPK activators in the HepG2 cell line. This result suggested AMPK activation by the mogroside aglycones 7 and 8 was proved to contribute at least partially to the anti-hyperglycemic and anti-lipidemic properties in vivo of S. grosvenorii. 相似文献
16.
Swati Gupta Gyanendra Pandey Neha Rahuja Arvind K. Srivastava Anil K. Saxena 《Bioorganic & medicinal chemistry letters》2010,20(19):5732-5734
A series of substituted phenoxy-3-piperazin-1-yl-propan-2-ols has been synthesized and evaluated for PTP1B inhibitory activity in vitro and for antidiabetic activity in vivo. Two molecules viz. 4a and 5b showed PTP1B inhibition of 31.58% and 35.90% at 100 μM concentration. The compound 4a also showed 40.3% normalization of plasma glucose levels at 100 mg/kg in Sugar-loaded model (SLM) and 32% activity in Streptozodocin model (STZ). The docking studies of these molecules revealed that hydrogen bond formation with Arg221 is important for activity. 相似文献
17.
A series of new benzothiazole-1,3,4-oxadiazole-4-thiazolidinone hybrid analogs (Tz1-Tz28) were synthesized in search of potential anti-diabetic agents. Molecular docking study was conducted with binding pocket of peroxisome proliferator activated receptor-gamma to elucidate the binding interactions of newly synthesized targets. Seven selected compounds with best docking scores were further screened for in vivo anti-hyperglycemic efficacy by oral glucose tolerance test in non-diabetic rats and on streptozotocin induced diabetic rat models. All the tested compounds demonstrated excellent to moderate reduction in blood glucose levels. Three of the compounds (Tz21, Tz7 and Tz10) showed excellent anti-diabetic effect by reducing concentration of glucose to 157.15 ± 1.79 mg/dL, 154.39 ± 1.71 mg/dL, 167.36 ± 2.45 mg/dL, respectively better than the standard drug, pioglitazone, 178.32 ± 1.88 mg/dL. Moreover, three derivatives Tz21, Tz4 and Tz24 with IC50 values of 0.21 ± 0.01 µM, 9.03 ± 0.12 µM and 11.96 ± 0.40 µM respectively also showed better inhibitory activities on alpha-glucosidase even more than the standard acarbose (IC50 = 18.5 ± 0.20 µM), indicating Tz21 has the highest inhibitory effect among the seven tested derivatives. Prediction of Drug like properties using molinspiration online software suggests that all the synthesized compounds have potential of becoming the orally active molecules. Thus, these novel hybrids could serve as potential candidates to become leads for the development of new drugs eliciting anti-hyperglycemic effect orally. 相似文献
18.
《Process Biochemistry》2014,49(10):1601-1605
The high concentration of total phenolic compounds (TPC) in Psidium guajava leaf extracts (GvEx) is correlated to its anti-hyperglycemic activity. In this study, we established the optimum ultrasound extraction conditions for maximizing TPC yield. The response surface methodology (RSM) was employed for empirical model building. The maximum value of TPC (26.12%) was obtained at solvent to solid ratio (v/w) of 12.1, extraction temperature of 59.8 °C, and extraction time of 5.1 min. The anti-hyperglycemic activity of GvEx was compared to the commonly used diabetic drug acarbose. The IC50 of GvEx for α-amylase and α-glucosidase inhibition was 50.5 μg/mL and 34.6 μg/mL, respectively. However, the IC50 of acarbose for α-amylase and α-glucosidase inhibition was 95.3 μg/mL and 1075.2 μg/mL, respectively. In conclusion, GvEx obtained under optimum extraction conditions had higher anti-hyperglycemic activity than acarbose. In addition, the recommended extraction procedures for GvEx save time and are environmentally friendly. 相似文献
19.
Makadia P Shah SR Pingali H Zaware P Patel D Pola S Thube B Priyadarshini P Suthar D Shah M Giri S Trivedi C Jain M Patel P Bahekar R 《Bioorganic & medicinal chemistry》2011,19(2):771-782
A novel series of thaizole and oxazole containing phenoxy acetic acid derivatives is reported as PPAR-pan agonists. Incorporation of structurally constrained oxime-ether based linker in the chemotype of a potent PPARδ selective agonist GW-501516 was adapted as designing strategy. In vitro, selected test compounds 12a, 12c, 17a and 18a showed PPAR-pan agonists activities and among these four compounds tested, 12a emerged as highly potent and efficacious compound, while 17a exhibited moderate and balanced PPAR-pan agonistic activity. In vivo, selected test compounds 12a and 17a exhibited significant anti-hyperglycemic and anti-hyperlipidemic activities in relevant animal models. These results support our hypothesis that the introduction of structurally constrained oxime-ether linker between lipophilic tail and acidic head plays an important role in modulating subtype selectivity and subsequently led to the discovery of potent PPAR-pan agonists. 相似文献
20.
QSAR analysis based on classical Hansch approach was adopted on two recently reported novel series of 2-phenylpyran-4-ones as selective cyclooxygenase-2 (COX-2) inhibitors. The 6-methyl derivatives of title compounds bifurcate as 3-phenoxypyran-4-ones (subset A) and 3-phenylpyran-4-ones (subset B) among series 1. Series 2 consists of 5-chloro derivatives of title compounds. Various regression equations were derived to study the influence of phenoxy and phenyl ring substituents of series 1 compounds on COX-2, COX-1 and selective COX-2 over COX-1 inhibitory activity. The best triparametric equation derived for 36 compounds of series 1 explains the hydrophobic, electronic and steric requirements for improved COX-2 inhibitory activity. QSAR model derived to explore the selective COX-2 over COX-1 inhibition showed that selectivity could be influenced by size and lipophilicity of substituents. The size of the first atom of 2 substituents appears to have negative effect on selectivity, whereas highly polar 3 substituents at R are favorable for improved selectivity. QSAR investigations on series 2 compounds revealed some interesting correlation of COX-2 inhibitory activity with calculated physicochemical properties of whole molecules. The positive logP confirms the hydrophobic interaction of series 2 compounds with COX-2 enzyme. The positive MR term indicates that an overall increase in size and polarizabilty of the molecules increases COX-2 inhibitory activity. The positive contribution of structural variable suggests biphenyl analogs are extremely potent COX-2 inhibitors. 相似文献