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1.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):88-92
Phytochemical investigations were performed on the EtOAc-soluble fraction of the whole plant of the sky flower (Duranta repens) which led to the isolation of the iridoid glycosides 1–6. Their structures were elucidated by both 1D and 2D NMR spectroscopic analysis. All the compounds showed potent antioxidative scavenging activity in four different tests, with half maximal inhibitory concentration (IC50) values in the range 0.481–0.719?mM against DPPH radicals, 4.07–17.21 µM for the hydroxyl radical (?OH) inhibitory activity test, 43.3–97.37 µM in the total reactive oxygen species (ROS) inhibitory activity test, and 3.39–18.94 µM in the peroxynitrite (ONOO?) scavenging activity test. Duranterectoside A (1) displayed the strongest scavenging potential with IC50 values of (0.481?±?0.06?mM, 4.07?±?0.03, 43.30?±?0.05, 3.39?±?0.02?µM) for the DPPH radicals, ?OH inhibitory activity test, total ROS inhibitory activity test and the ONOO? scavenging activity test, respectively. 相似文献
2.
Microwave‐assisted extraction was employed to extract polyphenols from the leaf of Magnolia kwangsiensis Figlar & Noot . The yield of polyphenols was 2.44±0.02 % under the optimal conditions of RSM: acetone concentration of 70 %, ratio of solvent to material of 21 mL?g?1 and extraction time of 16 min. The antioxidant activities were evaluated in terms of total antioxidant ability, reducing power, DPPH ? and ? OH scavenging activity. Results showed the polyphenols presented potential antioxidant activities, especially the stronger scavenging activity on ? OH. In term of ? OH scavenging activity, the IC50 value of NKA‐9 purification was 0.335 mg mL?1, equivalent to 35.23 % of VC. The IC50 values of crude extract and ethyl acetate extract were 0.580 and 0.828 mg mL?1, equivalent to 60.99 % and 87.07 % of VC. Results indicated that M. kwangsiensis leaf polyphenols present potential antioxidant activities that make it beneficial for human health by preventing or reducing oxidative damage. 相似文献
3.
Peter Lorenz Michael Zeh Jens Martens-Lobenhoffer Harry Schmidt Gerald Wolf 《Free radical research》2013,47(5):535-545
We investigated the antioxidant and radical scavenging activity of polyphenolic isochromans. To assess the relation between structure and scavenging properties the natural occurring 1-(3′-methoxy-4′-hydroxy)phenyl-6,7-dihydroxy-isochroman (ISO-3, three OH groups) was compared with three newly synthesized derivatives that differ in their degree of hydroxylation by substitution with methoxy-groups (ISO-4: four OH groups; ISO-2: two OH groups and ISO-0: fully methoxylated). We found that ISO-4 is a 2-fold better scavenger for the artificial radical 1,1-diphenyl-2-picrylhydrazyl (DPPH, 100?μM) with an EC50=10.3?μM compared to the natural ISO-3 (EC50=22.4?μM) and to ISO-2 (EC50=25.1?μM), while ISO-0 did not react with DPPH. The scavenging capacity for superoxide enzymatically generated in a hypoxanthin-xanthinoxidase reaction was the highest for ISO-4 (EC50=34.3?μM) compared to those of ISO-3 (EC50=84.0?μM) and ISO-2 (EC50=91.8?μM), while ISO-0 was inactive. In analogy, ISO-4 scavenged peroxynitrite (ONOO?, EC25=23.0?μM) more effective than ISO-3, ISO-2 and ISO-0.When C6 rat glioma cells loaded with the reactive oxygen/nitrogen (ROS/RNS)-sensitive fluorochrome 2,7-dichlorodihydrofluorescein, were exposed to hydrogen peroxide, the lowest stress level as indicated by the fluorescence signal was detected when the cells were pretreated with ISO-4 or ISO-2 but to a much lesser extent with ISO-3, while ISO-0 did not show any effect. All tested hydroxyisochromans superceded the scavenging effect of trolox.The excellent radical and ROS/RNS scavenging features of the hydroxy-1-aryl isochromans and their simple synthesis let these compounds appear to be interesting candidates for pharmaceutical interventions that protect against the deleterious action of ROS/RNS. 相似文献
4.
Hina Siddiqui Muhammad Arslan Bashir Kulsoom Javaid Arsalan Nizamani Huma Bano Sammer Yousuf 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):1392-1403
Tyramine derivatives 3–27 were synthesized by using conventional and environmental friendly ultrasonic techniques. These derivatives were then evaluated for the first time for their α-glucosidase (Sources: Saccharomyces cerevisiae and mammalian rat-intestinal acetone powder) inhibitory activity by using in vitro mechanism-based biochemical assays. Compounds 7, 14, 20, 21 and 26 were found to be more active (IC50?=?49.7?±?0.4, 318.8?±?3.7, 23.5?±?0.9, 302.0?±?7.3 and 230.7?±?4.0?μM, respectively) than the standard drug, acarbose (IC50?=?840.0?±?1.73?μM (observed) and 780?±?0.028?μM (reported)) against α-glucosidase obtained from Saccharomyces cerevisiae. Kinetic studies were carried out on the most active members of the series in order to determine their mode of inhibition and dissociation constants. Compounds 7, 20 and 26 were found to be the competitive inhibitors of α-glucosidase. These compounds were also screened for their protein antiglycation, and dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. Only compounds 20, 22 and 27 showed weak antiglycation activity with IC50 values 505.27?±?5.95, 581.87?±?5.50 and 440.58?±?2.74?μM, respectively. All the compounds were found to be inactive against DDP-IV enzyme. Inhibition of α-glucosidase, DPP-IV enzymes and glycation of proteins are valid targets for the discovery of antidiabetic drugs. Cytotoxicity of compounds 3–27 was also evaluated by using mouse fibroblast 3T3 cell lines. All the compounds were found to be noncytotoxic. The current study describes the synthesis α-glucosidase inhibitory activity of derivatives, based on a natural product tyramine template. The compounds reported here may serve as the starting point for the design and development of novel α-glucosidase inhibitors as antidiabetic agents. 相似文献
5.
Muhammad Taha Hayat Ullah Laode Muhammad Ramadhan Al Muqarrabun Muhammad Naseem Khan Fazal Rahim Norizan Ahmat Muhammad Tariq Javid Muhammad Ali Khalid Mohammed Khan 《Bioorganic & medicinal chemistry》2018,26(1):152-160
Bisindolylmethane thiosemicarbazides 1-18 were synthesized, characterized by 1H NMR and ESI MS and evaluated for urease inhibitory potential. All analogs showed outstanding urease inhibitory potentials with IC50 values ranging between 0.14?±?0.01 to 18.50?±?0.90?μM when compared with the standard inhibitor thiourea having IC50 value 21.25?±?0.90?μM. Among the series, analog 9 (0.14?±?0.01?μM) with di-chloro substitution on phenyl ring was identified as the most potent inhibitor of urease. The structure activity relationship has been also established on the basis of binding interactions of the active analogs. These binding interactions were identified by molecular docking studies. 相似文献
6.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):296-299
The bioassay-guided fractionation of H. oblongifolium has led to the isolation of potent urease inhibitors 1–3. The structures were elucidated by NMR and mass spectroscopic techniques. Compound 2 showed a potent enzyme inhibition activity (IC50 20.96?±?0.93), which is comparatively higher than that for the standard thiourea (IC50 21.01?±?0.51 μM). Compounds 1 and 3 also showed a significant activity, with IC50 37.95?±?1.93 and 138.43?±?1.23 μM, respectively. The sub crude fractions (F1, F2, F3, and F4) were tested in vitro for their urease inhibition activity. Fractions F2 and F4 showed significant activity with IC50 140.37?±?1.93 and 167.43?±?3.03 μM, respectively. 相似文献
7.
Guangcheng Wang Ming Chen Jie Qiu Zhenzhen Xie Anbai Cao 《Bioorganic & medicinal chemistry letters》2018,28(2):113-116
A novel series of chromone-isatin derivatives 6a–6p were designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS. These novel synthetic compounds were evaluated for inhibitory activity against yeast α-glucosidase enzyme. The results of biological test have shown that all tested compounds exhibited excellent to potent inhibitory activity in the range of IC50?=?3.18?±?0.12–16.59?±?0.17?μM as compared to the standard drug acarbose (IC50?=?817.38?±?6.27?μM). Compound 6j (IC50?=?3.18?±?0.12?μM) with a hydroxyl group at the 7-position of chromone and a 4-bromobenzyl group at the N1-positions of isatin, was found to be the most active compound among the series. Furthermore, molecular docking study was performed to help understand binding interactions of the most active analogs with α-glucosidase enzyme. These results indicated that this class of compounds had potential for the development of anti-diabetic agents. 相似文献
8.
Jang Hoon Kim Nguyen Phuong Thao Yoo Kyong Han Young Suk Lee Bui Thi Thuy Luyen Ha Van Oanh 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1174-1180
Cholinesterases (ChEs) are enzymes that break down neurotransmitters associated with cognitive function and memory. We isolated cinnamic acids (1 and 2), indolinones (3 and 4), and cycloartane triterpenoid derivatives (5–19) from the roots of Cimicifuga dahurica (Turcz.) Maxim. by chromatography. These compounds were evaluated for their inhibitory activity toward ChEs. Compound 1 was determined to have an IC50 value of 16.7?±?1.9?μM, and to act as a competitive inhibitor of acetylcholinesterase (AChE). Compounds 3, 4 and 14 were found to be noncompetitive with IC50 values of 13.8?±?1.5 and 6.5?±?2.5?μM, and competitive with an IC50 value of 22.6?±?0.4?μM, respectively, against butyrylcholinesterase (BuChE). Our molecular simulation suggested each key amino acid, Tyr337 of AChE and Asn228 of BuChE, which were corresponded with potential inhibitors 1, and 3 and 4, respectively. Compounds 1 and 4 were revealed to be promising compounds for inhibition of AChEs and BuChEs, respectively. 相似文献
9.
Fei Li Xi-Xi Guo Guang-Zhi Zeng Wei-Wei Qin Bo Zhang Ning-Hua Tan 《Bioorganic & medicinal chemistry letters》2018,28(14):2523-2527
To further investigate on the structure-activity relationships of immunosuppressive Astin C, seventeen analogues 1–17 were designed and synthetized via amino acid substitution strategy by the solid-phase peptide synthesis method for the first time. In comparison with Astin C (IC50?=?12.6?±?3.3?μM), only compounds 2 (IC50?=?38.4?±?16.2?μM), 4 (IC50?=?51.8?±?12.7?μM), 5 (IC50?=?65.2?±?15.6?μM), and 8 (IC50?=?61.8?±?12.4?μM) exhibited immunosuppressive activity in the Lymph node cells of mice. These results showed that the Astin C analogues containing D-amino acid residues, hydrophobic long-chain alkyl substituents, and aryl substituents performed better than those carrying hydrophilic amino acid residues and short-chain alkyl substituents. Moreover compounds 15, 16, and 17 had no immunosuppressive activity, which suggested that cis-3,4-dichlorinated proline played an important role in the immunosuppressive activity of Astin C. 相似文献
10.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):545-551
Aminopeptidase N (APN/CD13) over expressed on tumour cells, plays a critical role in tumour invasion, metastasis and tumour angiogenesis. In this article, we described the design, synthesis and preliminary activity studies of novel 3-amino-2-hydroxyl-3-phenylpropanoic acid derivatives as APN inhibitors. The in vitro enzymatic inhibitions on APN from porcine kidney showed that compound 7e had the most potent inhibitory activity against APN with the IC50 value to 1.26?±?0.01 μM, which is better than that of bestatin (IC50?=?2.55?±?0.11 μM). In addition, compound 7e also showed better inhibitory activity against APN on human ovary clear cell carcinoma cell ES-2 than bestatin with the IC50 value to 30.19?±?1.02 μM versus 60.61?±?0.1 μM. Compound 7e could be used as the lead compound in the future for anti-cancer agent research. 相似文献
11.
Yusuf Scak Emine Elin Oru‐Emre Mehmet
ztürk Tuba Takn‐Tok Ayegül Karaküük‐Iyidoan 《Chirality》2019,31(8):603-615
In this study, a series of fluorine‐containing chiral hydrazide‐hydrazone derivatives [III‐XII] from ?‐cysteine ethyl ester hydrochloride was synthesized as new antioxidant and anticholinesterase agents. The antioxidant activity of these derivatives was evaluated by ABTS+· and DPPH· scavenging and CUPRAC assays and the anticholinesterase activity by the Ellman method spectrophotometrically. The results of the antioxidant assay showed that compounds V , IX , and X exhibited higher activity than BHT and α‐tocopherol used as positive standards. Among the synthesized derivatives, compound IX (IC50: 2.3 ± 1.6 μM) exhibited higher acetylcholinesterase inhibitory activity than galantamine (IC50: 4.5 ± 0.8 μM). Compounds XI (IC50: 9.6 ± 1.0 μM), IX (IC50: 12.5 ± 1.6 μM), III (IC50: 16.0 ± 1.6 μM), X (IC50: 17.2 ± 1.8 μM), VI (IC50: 20.2 ± 0.8 μM), XII (IC50: 21.5 ± 1.0 μM), and VII (IC50: 24.6 ± 0.6 μM) displayed better butyrylcholinesterase inhibitory activity than galantamine (IC50: 46.03 ± 0.14 μM). ADME‐Tox analysis was used to probe the drug‐like properties of the compounds. Molecular docking studies were also applied to understand the interactions between compounds and targets. The docking calculations were supported by the experimental data. In particular, compound IX , having better activity than galantamine against acetylcholinesterase and butyrylcholinesterase enzymes, was visualized using molecular docking. 相似文献
12.
《Redox report : communications in free radical research》2013,18(2):95-102
Abstract Calendula officinalis (marigold) has many pharmacological properties. It is used for the treatment of skin disorders, pain and also as a bactericide, antiseptic and anti-inflammatory. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are known to participate in the pathogenesis of various human diseases and may be involved in the conditions which C. officinalis is used to treat. The aim of this study was to investigate the relationship between the beneficial properties of this plant and its antioxidant action. The butanolic fraction (BF) was studied because it is non-cytotoxic and is rich in a variety of bioactive metabolites including flavonoids and terpenoids. Superoxide radicals (O2?-) and hydroxyl radicals (HO?) are observed in decreasing concentrations in the presence of increasing concentrations of BF with IC50 values of 1.0 ± 0.09 mg/ml and 0.5 ± 0.02 mg/ml, respectively, suggesting a possible free radical scavenging effect. Lipid peroxidation in liver microsomes induced by Fe2+/ascorbate was 100% inhibited by 0.5 mg/ml of BF (IC50 = 0.15 mg/ml). Its total reactive antioxidant potential (TRAP) (in μM Trolox equivalents) was 368.14 ± 23.03 and its total antioxidant reactivity (TAR) was calculated to be 249.19 ± 14.5 μM. The results obtained suggest that the butanolic fraction of C. officinalis possesses a significant free radical scavenging and antioxidant activity and that the proposed therapeutic efficacy of this plant could be due, in part, to these properties. 相似文献
13.
Jinhui Hu Baijiao An Tingting Pan Zhengcunxiao Li Ling Huang Xingshu Li 《Bioorganic & medicinal chemistry》2018,26(21):5718-5729
A series of hybrids containing the pharmacophores of the histone deacetylase (HDAC) inhibitor, SAHA, and the antioxidant ebselen were designed and synthesized as multi-target-directed ligands against Alzheimer’s disease. An in vitro assay indicated that some of these molecules exhibit potent HDAC inhibitory activity and ebselen-related pharmacological effects. Specifically, the optimal compound 7f was found to be a potent HDAC inhibitor (IC50?=?0.037?μM), possessing rapid hydrogen peroxide scavenging activity and glutathione peroxidase-like activity (ν0?=?150.0?μM?min?1) and good free oxygen radical absorbance capacity (value of ORAC: 2.2). Furthermore, compound 7f showed significant protective effects against damage induced by H2O2 and the ability to prevent ROS accumulation in PC12 cells. 相似文献
14.
Rui Xu Ganyuan Xiao Yan Li Hongyan Liu Qing Song Xiaoyu Zhang Ziyi Yang Yunxiaozhu Zheng Zhenghuai Tan Yong Deng 《Bioorganic & medicinal chemistry》2018,26(8):1885-1895
A series of 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer’s disease (AD). The in vitro assays indicated that most of these derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compounds 11b and 11d displayed comprehensive advantages, with good AChE (IC50?=?0.29?±?0.01?μM and 0.46?±?0.02?μM, respectively), MAO-A (IC50?=?8.2?±?0.08?μM and 7.9?±?0.07?μM, respectively) and MAO-B (IC50?=?20.1?±?0.16?μM and 43.8?±?2.0% at 10?μM, respectively) inhibitory activities, moderate self-induced Aβ1–42 aggregation inhibitory potency (35.4?±?0.42% and 48.0?±?1.53% at 25?μM, respectively) and potential antioxidant activity. In addition, the two representative compounds displayed high BBB permeability in vitro. Taken together, these multifunctional properties make 11b and 11d as a promising candidate for the development of efficient drugs against AD. 相似文献
15.
Zeynep Soyer Sirin Uysal Sulunay Parlar Ayse Hande Tarikogullari Dogan Vildan Alptuzun 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):13-19
A series of 4-phthalimidobenzenesulfonamide derivatives were designed, synthesized and evaluated for the inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Structures of the title compounds were confirmed by spectral and elemental analyses. The cholinesterase (ChE) inhibitory activity studies were carried out using Ellman’s colorimetric method. The biological activity results revealed that all of the title compounds (except for compound 8) displayed high selectivity against AChE. Among the tested compounds, compound 7 was found to be the most potent against AChE (IC50=?1.35?±?0.08?μM), while compound 3 exhibited the highest inhibition against BuChE (IC50=?13.41?±?0.62?μM). Molecular docking studies of the most active compound 7 in AChE showed that this compound can interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. 相似文献
16.
Ya-Bing Xin Jia-Jun Li Hong-Jian Zhang Jun Ma Xin Liu 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1554-1564
To identify anticancer agents with high potency and low toxicity, a series of (Z)-styrylbenzene derivatives were synthesised and evaluated for anticancer activities using a panel of nine cancer cell lines and two noncancerous cell lines. Most derivatives exhibited significant anti-proliferative activities against five cancer cell lines, including MGC-803 and BEL-7402. (Z)-3-(p-Tolyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile (6h) showed a strong inhibitory effect on MGC-803 cells (IC50?0.01?µM) and exhibited stronger anti-proliferative activity than taxol (IC50?0.06?±?0.01?µM). The IC50 value of 6h in L-02 cells was 10,000-fold higher than in MGC-803 cells. Compound 6h inhibited proliferation of BEL-7402 cells by arresting at the G2/M phase through up-regulation of cyclin B1 expression, down-regulation of cyclin A and D1 expression, and induction of apoptosis. In addition, 6h inhibited the migration of BEL-7402 cells and the formation of cell colonies. 相似文献
17.
Ling Feng Yu Zhang Yan-Chun Liu Yan Liu Shi-Hong Luo Chun-Shuai Huang Sheng-Hong Li 《Bioorganic & medicinal chemistry》2019,27(2):442-446
A new flavoalkaloid racemate, leucoflavonine (1), together with its flavonoid precursor pectolinarigenin (2), was isolated from the leaves of Leucosceptrum canum collected from Tibet. Its structure was established by comprehensive spectroscopic analysis. Chrial separation of the enantiomers of 1 was achieved, and their absolute configurations were determined as S-(+)- and R-(?)-leucoflavonines ((+)-1a and (?)-1b) by comparison of their computational and experimental optical rotations. Biological assays indicated that both (+)-1a and (?)-1b exhibited inhibitory activity against acetylchlorinesterase (AChE) in vitro (IC50?=?68.0?±?8.6 and 18.3?±?1.8?μM, respectively). Moreover, (?)-1b displayed cytotoxicity against human hepatoma cells HepG2 (IC50?=?52.9?±?3.6?μM), and inhibited the production of interleukelin-2 (IL-2) in Jurkat cells (IC50?=?16.5?±?0.9?μM), while (+)-1a showed no obvious activity in these assays. 相似文献
18.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):773-778
The CHCl3-soluble fraction of the whole plant of Duranta repens showed anti-plasmodial activity against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum, with IC50 values of 8.5?±?0.9 and 10.2?±?1.5?μg/mL, respectively. From this fraction, two new flavonoid glycosides, 7-O-α-d-glucopyranosyl-3,4′-dihydroxy-3′-(4-hydroxy-3-methylbutyl)-5,6-dimethoxyflavone (1) and 7-O-α-d-glucopyranosyl(6′′′-p-hydroxcinnamoyl)-3,4′-dihydroxy-3′-(4-hydroxy-3-methylbutyl)-5,6-dimethoxyflavone (2), along with five known flavonoids, 3,7,4′-trihydroxy-3′-(4-hydroxy-3-methylbutyl)-5,6-dimethoxyflavone (3), 3,7-dihydroxy-3′-(4-hydroxy-3-methylbutyl)-5,6,4′-trimethoxyflavone (4), 5,7-dihydroxy-3′-(2-hydroxy-3-methyl-3-butenyl)-3,6,4′-trimethoxyflavone (5), 3,7-dihydroxy-3′-(2-hydroxy-3-methyl-3-buten-yl)-5,6,4′-trimethoxyflavone (6), and 7-O-α-d-glucopyranosyl-3,5-dihydroxy-3′-(4′′-acetoxy-3′′-methylbutyl)-6,4′-dimethoxyflavone (7), have been isolated as anti-plasmodial principles. Their structures were deduced by spectroscopic analysis including 1D and 2D NMR techniques. The compounds (1–7) showed potent anti-plasmodial activities against D6 and W2 strains of Plasmodium falciparum, with IC50 values in the range of 5.2–13.5?μM and 5.9–13.1?μM, respectively. 相似文献
19.
IJAZ AHMAD SHILIN CHEN YONG PENG SIBAO CHEN LIJIA XU 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):140-143
Phytochemical investigations on the ethyl acetate-soluble fraction of the whole plant of Buddleja crispa led to the isolation of the iridoids 1–7. Compound 2 displayed significant inhibitory potential against enzyme lipoxygenase in a concentration-dependant fashion with IC50 value of 39.7 ± 0.02μM, along with DPPH radical scavenging activity with IC50 value 0.638 mM. 相似文献
20.
Wenwen Liu Huan Wang Xiaokang Li Yixiang Xu Jian Zhang Wei Wang Qi Gong Xiaoxia Qiu Jin Zhu Fei Mao Haiyan Zhang Jian Li 《Bioorganic & medicinal chemistry》2018,26(12):3117-3125
Depression, a severe mental disease, is greatly difficult to treat and easy to induce other neuropsychiatric symptoms, the most frequent one is cognitive impairment. In this study, a series of novel vilazodone-tacrine hybrids were designed, synthesized and evaluated as multitarget agents against depression with cognitive impairment. Most compounds exhibited good multitarget activities and appropriate blood-brain barrier permeability. Specifically, compounds 1d and 2a exhibited excellent 5-HT1A agonist activities (1d, EC50?=?0.36?±?0.08?nM; 2a, EC50?=?0.58?±?0.14?nM) and 5-HT reuptake inhibitory activities (1d, IC50?=?20.42?±?6.60?nM; 2a, IC50?=?22.10?±?5.80?nM). In addition, they showed moderate ChE inhibitory activities (1d, AChE IC50?=?1.72?±?0.217?μM, BuChE IC50?=?0.34?±?0.03?μM; 2a, AChE IC50?=?2.36?±?0.34?μM, BuChE IC50?=?0.10?±?0.01?μM). Good multitarget activities with goodt blood-brain barrier permeability of 1d and 2a make them good lead compounds for the further study of depression with cognitive impairment. 相似文献