排序方式: 共有27条查询结果,搜索用时 15 毫秒
1.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):1105-1112
Nine novel 4-[3-(4-Dimethylamino-phenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl]-benzenesulfonamides (2a-i) were synthesized and evaluated for their anti-inflammatory and antiproliferative activities. These compounds (2a-i) showed moderate to strong anti-inflammatory activity in carrageenan rat paw oedema test. Compounds 2b, 2d and 2g showing comparable anti-inflammatory activity to that of reference drug celecoxib were evaluated for their ulcerogenic and analgesic activities. The effect of 2b, 2d and 2g on the content of NO, TNF-α and PGE2 in exudates from rat paw stimulated by carrageenan was also evaluated. The compound 2c showed considerable antitumor activities against all 60 human tumor cell lines with effective GI50 (MG-MID) value of 3.63 µM. It exhibited maximum activity against melanoma (LOX IMVI and SK-MEL-5) cancer cell lines with GI50 value less than 2 μM. 相似文献
2.
Adnan A. Bekhit Eskedar T. Lodebo Ariaya Hymete Hanan M. Ragab Salma A. Bekhit Kikuko Amagase Afnan Batubara Mohammed A. S. Abourehab Alaa El-Din A. Bekhit Tamer M. Ibrahim 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):2320
Promising inhibitory activities of the parasite multiplication were obtained upon evaluation of in vivo antimalarial activities of new pyrazolylpyrazoline derivatives against Plasmodium berghei infected mice. Further evaluation of 5b and 6a against chloroquine-resistant strain (RKL9) of P. falciparum showed higher potency than chloroquine. In vitro antileishmanial activity testing against Leishmania aethiopica promastigote and amastigote forms indicated that 5b, 6a and 7b possessed promising activity compared to miltefosine and amphotericin B deoxycholate. Moreover, antileishmanial activity reversal of the active compounds via folic and folinic acids showed comparable results to the positive control trimethoprim, indicating an antifolate mechanism via targeting leishmanial DHFR and PTR1. The compounds were non-toxic at 125, 250 and 500 mg/kg. In addition, docking of the most active compound against putative malarial target Pf-DHFR-TS and leishmanial PTR1 rationalised the observed activities. Molecular dynamics simulations confirmed a stable and high potential binding of 7a against leishmanial PTR1. 相似文献
3.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):565-571
The synthesis of a new series of 1-[(benzazole-2-yl)thioacetyl]-3,5-diaryl-2-pyrazoline derivatives was obtained by reacting 1-(chloroacetyl)-3,5-diaryl-pyrazolines with 2-mercaptobenzimidazole/benzoxazole/benzothiazole. The chemical structures of the compounds were elucidated by 1H-NMR, 13C-NMR, and FAB+-MS spectral data. Their antifungal activities against Candida albicans, Candida glabrata, Candida utilis, Candida tropicalis, Candida krusei, and Candida parapsilosis were investigated. A significant level of activity was observed. 相似文献
4.
Mohammad Abdel-Halim Adam B. Keeton Evrim Gurpinar Bernard D. Gary Simon M. Vogel Matthias Engel Gary A. Piazza Frank M. Boeckler Rolf W. Hartmann Ashraf H. Abadi 《Bioorganic & medicinal chemistry》2013,21(23):7343-7356
Derivatives with scaffolds of 1,3,5-tri-substituted pyrazoline and 1,3,4,5-tetra-substituted pyrazoline were synthesized and tested for their inhibitory effects versus the p53+/+ HCT116 and p53?/? H1299 human tumor cell lines. Several compounds were active against the two cell lines displaying IC50 values in the low micromolar range with a clearly more pronounced effect on the p53+/+ HCT116 cells. The compound class shows excellent developability due to the modular synthesis, allowing independent optimization of all three to four key substituents to improve the properties of the molecules. 相似文献
5.
The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC50: 0.68 ± 0.13 μM) with strong DPPH and ABTS radical scavenging activity (IC50: 13.77 ± 0.25 μM and IC50: 12.59 ± 0.21 μM), respectively. While P3 exhibited as the second most potent compound with AChE inhibition (IC50: 0.74 ± 0.09 μM) and with DPPH and ABTS radical scavenging activity (IC50: 13.52 ± 0.62 μM and IC50: 13.13 ± 0.85 μM), respectively. Finally, molecular docking studies provided prospective evidence to identify key interactions between the active inhibitors and the AChE that furthermore led us to the identification of plausible binding mode of novel indolopyrazoline derivatives. Additionally, in-silico ADME prediction using QikProp shows that these derivatives fulfilled all the properties of CNS acting drugs. This study confirms the first time reporting of indolopyrazoline derivatives as potential anti-Alzheimer agents. 相似文献
6.
Dharam Pal Pathak Vidushi Sharma Sachin Kumar 《Bioorganic & medicinal chemistry letters》2018,28(9):1566-1569
Coumarin containing pyrazoline derivatives have been synthesized and tested as inhibitors of in vitro development of a chloroquine-sensitive (MRC-02) and chloroquine-resistant (RKL-2) strain of Plasmodium falciparum and in vivo Plasmodium berghei malaria. Docking study was also done on cysteine protease falcipain-2 which showed that the binding pose of C-14 molecule and epoxysuccinate, inhibitor of falcipain-2, binds in the similar pattern. The most active antimalarial compound was 3-(1-benzoyl-5-(4-flurophenyl)-4,5-dihydro-1H-pyrazol-3yl)-7-(diethyamino)-2H-chromen-2-one C-14, with an IC50 of 4.21?µg/ml provided complete protection to the infected mice at 24?mg/kg X 4?days respectively. 相似文献
7.
Two new series of 4,6-diaryl-3-cyanopyridine 4a-r and 1,3,5-triaryl-2-pyrazolines 6a-f and were prepared. The new compounds were evaluated for their in vitro COX-2 selectivity and in vivo anti-inflammatory activity. Compounds 4o,r and 6d,f had moderate to high selectivity index (S.I.) compared to celecoxib (selectivity indexes of 4.5, 3.14, 4.79 and 3.21, respectively) and also, showed in vivo anti-inflammatory activity approximately equal to or higher than celecoxib (edema inhibition % = 60.5, 64.5, 59.3 and 59.3, after 3 h, respectively) and the effective anti-inflammatory doses were (ED50 = 10.1, 7.8, 8.46 and 10.7 mg/kg respectively, celecoxib ED50 = 10.8 mg/kg) and ulcerogenic liability were determined for these compounds which showed promising activity by being more potent than celecoxib with nearly negligible ulcerogenic liability compared to celecoxib (reduction in ulcerogenic liability versus celecoxib = 85, 82, 74 and 67%, respectively). 相似文献
8.
S.N. Suryawanshi Avinash Tiwari Santosh Kumar Rahul Shivahare Monika Mittal Padam Kant Suman Gupta 《Bioorganic & medicinal chemistry letters》2013,23(10):2925-2928
A novel series of triazole integrated phenyl heteroterpenoids have been synthesized and screened for their in vitro activity against intracellular amastigote form of Leishmania donovani. Among all tested compounds, compound 3a was found to be the most active with IC50 6.4 μM and better selectivity index (SI) 18 as compared to reference drugs, miltefosine and miconazole. When evaluated in vivo in L. donovani/hamster model, 3a has exhibited 79 ± 11% inhibition of parasite multiplication at 50 mg kg?1 × 5 days on day 7 post treatment. 相似文献
9.
Ferreras JA Gupta A Amin ND Basu A Sinha BN Worgall S Jayaprakash V Quadri LE 《Bioorganic & medicinal chemistry letters》2011,21(21):6533-6537
Mycobacterium tuberculosis (Mtb) and Yersinia pestis (Yp) produce siderophores with scaffolds of nonribosomal peptide-polyketide origin. Compounds with structural similarities to these siderophores were synthesized and evaluated as antimicrobials against Mtb and Yp under iron-limiting conditions mimicking the iron scarcity these pathogens encounter in the host and under standard iron-rich conditions. Several new antimicrobials were identified, including some with increased potency in the iron-limiting condition. Our study illustrates the possibility of screening compound libraries in both iron-rich and iron-limiting conditions to identify antimicrobials that may selectively target iron scarcity-adapted bacteria and highlights the usefulness of building combinatorial libraries of compounds having scaffolds with structural similarities to siderophores to feed into antimicrobial screening programs. 相似文献
10.
In an effort to develop selective MAO (monoamine oxidase) B inhibitors, structure based virtual screening was initiated on an in-house library. Top 10 HITS were synthesized and evaluated for MAO (A and B) inhibitory activity, both against human and rat enzymes. All the compounds were found selective, reversible and active in nM range (100 times more potent than selegeline) towards MAO-B. Outstanding co-relation between predicted and experimental Ki values were observed. 相似文献