Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 40
Filter
Add more filters










Publication year range
1.
Mol Divers ; 2023 Mar 23.
Article in English | MEDLINE | ID: mdl-36959424

ABSTRACT

A series of 4-methyl-5-(3-phenylacryloyl)thiazoles based on chalcones were designed, synthesized and evaluated for their influenza neuraminidase (NA) inhibitory activity in vitro. A preliminary structure-activity relationship (SAR) analysis showed that thiazoles bearing amide had greater potency. It also showed that mono-hydroxyl group at 4-position on phenyl ring was more effective than other electron-releasing groups or electron-withdraw groups. Compounds A2 and A26 were more potent against NA with IC50 values of 8.2 ± 0.5 µg/mL and 6.2 ± 1.4 µg/mL, respectively. Molecular docking study demonstrated that thiazoles skeleton was benefit for the NA inhibitory activity.

2.
Org Biomol Chem ; 19(48): 10611-10616, 2021 12 15.
Article in English | MEDLINE | ID: mdl-34854450

ABSTRACT

A convenient and efficient method for the generation of the iminoxy radical through anodic oxidation was developed for the synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from N-benzyl amidoximes. The transformation proceeds through 1.5-Hydrogen Atom Transfer (1,5-HAT) and intramolecular cyclization. The process features simple operation, mild conditions, broad substrate scope and high functional group compatibility, and provides a facile and practical way for the preparation of 1,2,4-oxadiazoles.

3.
Eur J Med Chem ; 213: 113161, 2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33540229

ABSTRACT

A series of 4-thiazolinone derivatives (D1-D58) were designed and synthesized. All of the derivatives were evaluated in vitro for neuraminidase (NA) inhibitory activities against influenza virus A (H1N1), and the inhibitory activities of the five most potent compounds were further evaluated on NA from two different influenza viral subtypes (H3N2 and B), and then their in vitro anti-viral activities were evaluated using the cytopathic effect (CPE) reduction assay. The results showed that the majority of the target compounds exhibited moderate to good NA inhibitory activity. Compound D18 presented the most potent inhibitory activity with IC50 values of 13.06 µM against influenza H1N1 subtype. Among the selected compounds, D18 and D41 turned out to be the most potent inhibitors against influenza virus H3N2 subtype (IC50 = 15.00 µM and IC50 = 14.97 µM, respectively). D25 was the most potent compound against influenza B subtype (IC50 = 16.09 µM). In addition, D41 showed low toxicity and greater potency than reference compounds Oseltamivir and Amantadine against N1-H275Y variant in cellular assays. The structure-activity relationship (SAR) analysis showed that introducing 4-CO2H, 4-OH, 3-OCH3-4-OH substituted benzyl methylene can greatly improve the activity of 4-thiazolinones. Further SAR analysis indicated that 4-thiazolinone and ferulic acid fragments are necessary fragments of target compounds for inhibiting NA. Molecular docking was performed to study the interaction between compound D41 and the active site of NA. This study may providing important information for new drug development for anti-influenza virus including mutant influenza virus.


Subject(s)
Antiviral Agents/pharmacology , Drug Design , Enzyme Inhibitors/pharmacology , Influenza A Virus, H3N2 Subtype/drug effects , Neuraminidase/antagonists & inhibitors , Thiazoles/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Influenza A Virus, H3N2 Subtype/enzymology , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Structure , Neuraminidase/metabolism , Structure-Activity Relationship , Thiazoles/chemical synthesis , Thiazoles/chemistry
4.
Bioorg Chem ; 106: 104469, 2021 01.
Article in English | MEDLINE | ID: mdl-33239239

ABSTRACT

A series of novel 2-oxoquinoline derivatives containing arylaminothiazole were designed and synthesized as potential antitumor agents. The synthesized compounds were evaluated for their in vitro cytotoxicity activity against HeLa, NCI-H460, T24 and SKOV3 cancer cell lines using MTT assay. Among them, compound A7 exhibited the most potent activity against the test cancer cell lines, with the IC50 values ranged from 4.4 to 8.7 µM. The results of tubulin polymerization assay showed that compound A7 could inhibit tubulin polymerization in vitro. Meanwhile, molecular docking study revealed that A7 can bind to the colchicine site of tubulin and formed hydrogen bonds with key amino acid residues in the active site. Further mechanism study demonstrated that compound A7 blocked cell cycle arrest at G2/M phase, induced cell apoptosis and depolarized mitochondria of HeLa cells. Collectively, our findings suggest that A7 could serve as a promising lead for the development of more efficient microtubule polymerization inhibitors for cancer therapy.


Subject(s)
Antineoplastic Agents/pharmacology , Quinolones/pharmacology , Thiazoles/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/metabolism , Apoptosis/drug effects , Binding Sites , Cattle , Cell Line, Tumor , Drug Design , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Molecular Docking Simulation , Protein Binding , Quinolones/chemical synthesis , Quinolones/metabolism , Rats , Thiazoles/chemical synthesis , Thiazoles/metabolism , Tubulin/chemistry , Tubulin/metabolism , Tubulin Modulators/chemical synthesis , Tubulin Modulators/metabolism , Tubulin Modulators/pharmacology
5.
Arch Pharm (Weinheim) ; 353(1): e1900174, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31657061

ABSTRACT

Four series of ferulic acid derivatives were designed, synthesized, and evaluated for their neuraminidase (NA) inhibitory activities against influenza virus H1N1 in vitro. The pharmacological results showed that the majority of the target compounds exhibited moderate influenza NA inhibitory activity, which was also better than that of ferulic acid. The two most potent compounds were 1m and 4a with IC50 values of 12.77 ± 0.47 and 12.96 ± 1.34 µg/ml, respectively. On the basis of the biological results, a preliminary structure-activity relationship (SAR) was derived and discussed. Besides, molecular docking was performed to study the possible interactions of compounds 1p, 2d, 3b, and 4a with the active site of NA. It was found that the 4-OH-3-OMe group and the amide group (CON) of ferulic acid amide derivatives were two key pharmacophores for NA inhibitory activity. It is meaningful to further modify the natural product ferulic acid to improve its influenza NA inhibitory activity.


Subject(s)
Antiviral Agents/pharmacology , Biological Assay , Coumaric Acids/pharmacology , Enzyme Inhibitors/pharmacology , Influenza A Virus, H1N1 Subtype/drug effects , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Coumaric Acids/chemical synthesis , Coumaric Acids/chemistry , Crystallography, X-Ray , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Influenza A Virus, H1N1 Subtype/enzymology , Microbial Sensitivity Tests , Models, Molecular , Molecular Structure , Neuraminidase/antagonists & inhibitors , Neuraminidase/metabolism , Structure-Activity Relationship
6.
Bioorg Med Chem ; 27(16): 3729-3734, 2019 08 15.
Article in English | MEDLINE | ID: mdl-31278004

ABSTRACT

As a known natural product with anti-tumor activity, honokiol has been widely researched and structural modified. Lots of honokiol derivatives have been found to possess good anti-proliferative activity and showed great potential in cancer therapy, but the SAR (structure-activity relationship) was still confused. Here in, the SAR were comprehensively researched by summary of reported derivatives and synthesis of novel derivatives. Amongst novel derivatives, the promising compounds A6 and A10 exhibited potent and selective anti-proliferative activities against K562 cell line with the IC50 values of 5.04 and 7.08 µM respectively. The SAR was discussed around honokiol and 79 derivatives by the means of CoMFA and theoretical calculation, which provided useful suggestion for further structural optimization of honokiol derivatives.


Subject(s)
Biphenyl Compounds/therapeutic use , Lignans/therapeutic use , Biphenyl Compounds/pharmacology , Humans , Lignans/pharmacology , Structure-Activity Relationship
7.
Bioorg Med Chem ; 27(15): 3218-3228, 2019 08 01.
Article in English | MEDLINE | ID: mdl-31160140

ABSTRACT

Diflumetorim is a member of pyrimidinamine fungicides that possess excellent antifungal activities. Nevertheless, as reported that the activity of diflumetorim to corn rust (Puccinia sorghi) was not ideal (EC50 = 53.26 mg/L). Herein, a series of novel pyrimidinamine derivatives containing phenyl-thiazole/oxazole moiety were designed based on our previous study and the structural characteristics of diflumetorim, synthesized and bioassayed to discover novel fungicides with excellent antifungal activities. Among these compounds, T18 gave the optimal fungicidal activity, which respectively offers control effects with EC50 values of 0.93 mg/L against P. sorghi and 1.24 mg/L against E. graminis, significantly superior to commercial fungicides diflumetorim, tebuconazole, and flusilazole. Cell cytotoxicity results suggested that compound T18 has lower toxicities than diflumetorim. Furthermore, DFT calculation indicated that the phenyl-thiazole/oxazole moiety plays an unarguable role in the improvement of activity, which will contribute to designing and developing more potent compounds in the future.


Subject(s)
Antifungal Agents/pharmacology , Drug Design , Fungicides, Industrial/pharmacology , Oxazoles/pharmacology , Pyrimidines/pharmacology , Thiazoles/pharmacology , Alternaria/drug effects , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Ascomycota/drug effects , Botrytis/drug effects , Density Functional Theory , Dose-Response Relationship, Drug , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Gibberella/drug effects , Microbial Sensitivity Tests , Molecular Structure , Oxazoles/chemistry , Phytophthora/drug effects , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Structure-Activity Relationship , Thiazoles/chemistry
8.
Pestic Biochem Physiol ; 154: 78-87, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30765060

ABSTRACT

A series of novel aryloxyphenoxypropionate (APP) herbicides containing benzofuran moiety were designed, synthesized and tested for herbicidal activity. The bioassay results indicated that most of target compounds possessed moderate to good herbicidal activity against monocotyledonous weeds. Compounds 5a-5d and 6a-6d showed 100% control efficiency against crabgrass (Digitaria sanguinalis) and barnyard grass (Echinochloa crus-galli) in both pre-emergence and post-emergence treatments at the dosage of 1500 g a.i. ha-1. Compound 6c was the most promising, with herbicidal activity better than clodinafop-propargyl. Molecular docking for compound 6c and its hydrolysis acid 1c were performed. ACCase activities of some compounds were also tested. Theoretical calculations for corresponding hydrolysis products 1a-1ewere carried out. Based on the results of molecular docking, enzyme activity test and theoretical calculation, the potential mechanism for herbicidal activity of these compounds was evaluated.


Subject(s)
Benzofurans/pharmacology , Herbicides/pharmacology , Propionates/pharmacology , Acetyl-CoA Carboxylase/metabolism , Benzofurans/chemistry , Digitaria/drug effects , Digitaria/physiology , Drug Design , Echinochloa/drug effects , Echinochloa/physiology , Herbicides/chemistry , Models, Theoretical , Molecular Docking Simulation , Plant Proteins/metabolism , Plant Weeds/drug effects , Propionates/chemistry
9.
J Asian Nat Prod Res ; 21(11): 1052-1067, 2019 Nov.
Article in English | MEDLINE | ID: mdl-30585512

ABSTRACT

Honokiol, a natural polyphenol, which was reported to have satisfactory influenza neuraminidase (NA) inhibitory activity, was structurally modified. Twenty-three compounds were synthesized and the ortho-effects in the epoxidation and hydrolyzation reactions were studied. The derivatives were evaluated for NA inhibitory activity and the benzoylhydrazone derivatives showed much better anti-NA activity than honokiol. Structure-activity relationship analysis suggested that the polyphenols exhibited better anti-NA activity than monophenols and biphenols. Furthermore, probable binding mode of drug with target revealed that the most active compound had much stronger interactions with the active site of NA than honokiol suggesting the potent anti-influenza virus activity.


Subject(s)
Antiviral Agents , Influenza, Human , Biphenyl Compounds , Drug Design , Humans , Lignans , Molecular Structure , Neuraminidase
10.
Bioorg Med Chem ; 26(22): 5974-5985, 2018 12 01.
Article in English | MEDLINE | ID: mdl-30401501

ABSTRACT

Multidrug resistance (MDR) has been shown to reduce the effectiveness of chemotherapy. Strategies to overcoming MDR have been widely explored in the last decades, leading to a generation of numerous small molecules targeting ABC and MRP transporters. Among the ABC family, ABCB1 plays key roles in the development of drug resistance and is the most well studied. In this work, we report the discovery of non-toxic [1,2,4]triazolo[1,5-a]pyrimidin-7-one (WS-10) from our structurally diverse in-house compound collection that selectively modulates ABCB1-mediated multidrug resistance. WS-10 enhanced the intracellular accumulation of paclitaxel in SW620/Ad300 cells, but did not affect the expression of ABCB1 Protein and ABCB1 localization. The cellular thermal shift assay (CETSA) showed that WS-10 was able to bind to ABCB1, which could be responsible for the reversal effect of WS-10 toward paclitaxel and doxorubicin in SW620/Ad300 cells. Docking simulations were performed to show the possible binding modes of WS-10 within ABCB1 transporter. To conclude, WS-10 could be used as a template for designing new ABCB1 modulators to overcome ABCB1-mediated multidrug resistance.

11.
Bioorg Med Chem ; 26(18): 5006-5017, 2018 10 01.
Article in English | MEDLINE | ID: mdl-30150104

ABSTRACT

Multidrug resistance (MDR) has been shown to reduce the effectiveness of chemotherapy. Strategies to overcoming MDR have been widely explored in the last decades, leading to a generation of numerous small molecules targeting ABC and MRP transporters. Among the ABC family, ABCB1 plays key roles in the development of drug resistance and is the most well studied. In this work, we report the discovery of a non-toxic [1,2,4]triazolo[1,5-a]pyrimidin-7-one (WS-10) from our structurally diverse in-house compound collection that selectively modulates ABCB1-mediated multidrug resistance. WS-10 enhanced the intracellular accumulation of paclitaxel in SW620/Ad300 cells, but did not affect the expression of ABCB1 Protein and ABCB1 localization. The cellular thermal shift assay (CETSA) showed that WS-10 was able to bind to ABCB1, which could be responsible for the reversal effect of WS-10 toward paclitaxel and doxorubicin in SW620/Ad300 cells. Docking simulations were performed to show the possible binding modes of WS-10 within ABCB1 transporter. To conclude, WS-10 could be used as a template for designing new ABCB1 modulators to overcome ABCB1-mediated multidrug resistance.


Subject(s)
Azoles/pharmacology , Drug Resistance, Multiple/drug effects , Pyrimidines/pharmacology , ATP Binding Cassette Transporter, Subfamily B/drug effects , ATP Binding Cassette Transporter, Subfamily B/physiology , Antineoplastic Agents, Phytogenic/pharmacology , Azoles/chemistry , Cell Line, Tumor , Humans , Inhibitory Concentration 50 , Paclitaxel/pharmacology , Pyrimidines/chemistry
13.
Eur J Med Chem ; 149: 170-181, 2018 Apr 10.
Article in English | MEDLINE | ID: mdl-29501939

ABSTRACT

Pyrazolecarboxamide fungicides are one of the most important classes of agricultural fungicides, which belong to succinodehydrogenase inhibitors (SDHIS). To discover new pyrazolecarboxamide analogues with broad spectrum and high activity, a class of new compounds of pyrazole carboxamide derivatives containing thiazole or oxazole ring were designed by scaffold hopping and bioisosterism, and 36 pyrazole carboxamide derivatives with antifungal activity were synthesized. Those compounds were evaluated against five phytopathogenic fungi, Gibberella zeae, Phytophythora capsici, Sclerotonia sclerotiorum, Erysiphe graminis and Puccinia sorghi. The results indicated that most of the compounds displayed good fungicidal activities, especially against E. graminis. Theoretical calculations were carried out at the B3LYP/6-31G (d, p) level and the full geometry optimization was carried out using the 6-31G (d, p) basis set, and the frontier orbital energy, atomic net charges, molecular docking were discussed, and the structure-activity relationships were also studied.


Subject(s)
Antifungal Agents/chemical synthesis , Oxazoles/chemistry , Pyrazoles/chemical synthesis , Thiazoles/chemistry , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Fungi/drug effects , Models, Chemical , Models, Theoretical , Molecular Docking Simulation , Pyrazoles/pharmacology , Structure-Activity Relationship
14.
RSC Adv ; 8(60): 34331-34342, 2018 Oct 04.
Article in English | MEDLINE | ID: mdl-35548655

ABSTRACT

5-Arylbenzofuran neolignans, a newfound class of natural products, were reported to possess several kinds of pharmacological activities. To solve the lack of natural sources and promote the research of 5-arylbenzofuran neolignans in all fields, an available semi-synthesis methodology of 5-arylbenzofuran neolignans was developed, and a detailed structural modification was conducted. In the meantime, a one-pot process of Waker-type cyclization and Wacker-type oxidation was developed. To explore the potential of 5-arylbenzofuran neolignans as bioactive substances, 5-arylbenzofuran neolignans and their derivatives were evaluated for their cytotoxicity. As a result, a preliminary structure-activity relationship was obtained. Most derivatives revealed low cytotoxic effects suggesting that they were relatively safer than the natural 5-arylbenzofuran neolignan. Several derivatives showed high cytotoxicities which were found to be closely associated with apoptosis-inducing. The selectivity assay for cytotoxicity showed tumor cells were more sensitive to the promising compounds than normal cells.

15.
Mol Divers ; 21(3): 565-576, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28536876

ABSTRACT

Two series of novel 2-thiazolylhydrazone derivatives were designed and synthesized via one-pot reaction of benzaldehyde derivatives, [Formula: see text]-haloketones and thiosemicarbazide. The structures of compounds 1 and 2 were characterized by [Formula: see text] NMR and [Formula: see text] NMR, and compound 1g was further confirmed by X-ray crystallography. All of the target compounds were evaluated for their NA inhibitory activity against influenza viral neuraminidase (H1N1) in vitro, and the results showed that many compounds exhibited moderate to strong inhibitory activities against influenza viral neuraminidase (H1N1). Among them, compounds 1p, 1q and 2c showed the most potent inhibitory activities with [Formula: see text] values ranging from 10.50 to [Formula: see text]. Our structure-activity relationship analysis indicated that 2-thiazolylhydrazone is an effective scaffold for NA inhibitors and that introducing an ethoxycarbonyl group to the 5-position of thiazole ring could enhance inhibitory potency. Molecular docking was performed on the most active compounds 1p and 2c to provide more insight into their mechanism of interaction.


Subject(s)
Enzyme Inhibitors/chemical synthesis , Hydrazones/chemical synthesis , Influenza A Virus, H1N1 Subtype/enzymology , Neuraminidase/antagonists & inhibitors , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Crystallography, X-Ray , Drug Design , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Hydrazones/chemistry , Hydrazones/pharmacology , Influenza A Virus, H1N1 Subtype/drug effects , Inhibitory Concentration 50 , Molecular Docking Simulation , Molecular Structure , Structure-Activity Relationship , Thiazoles/chemical synthesis , Thiazoles/chemistry , Thiazoles/pharmacology
16.
Int J Mol Sci ; 17(5)2016 Apr 29.
Article in English | MEDLINE | ID: mdl-27136538

ABSTRACT

With the aim of discovering new anticancer agents, we have designed and synthesized novel α-aminophosphonate derivatives containing a 2-oxoquinoline structure using a convenient one-pot three-component method. The newly synthesized compounds were evaluated for antitumor activities against the A549 (human lung adenocarcinoma cell), HeLa (human cervical carcinoma cell), MCF-7 (human breast cancer cell), and U2OS (human osteosarcoma cell) cancer cell lines in vitro, employing a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The results of pharmacological screening indicated that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most compounds showed more potent inhibitory activities comparable to 5-fluorouracil (5-FU) which was used as a positive control. The mechanism of representative compound 4u (diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(phenyl-amino)methyl)phosphonate) indicated that the compound mainly arrested HeLa cells in S and G2 stages and was accompanied by apoptosis in HeLa cells. This action was confirmed by acridine orange/ethidium bromide staining, Hoechst 33342 staining, and flow cytometry.


Subject(s)
Antineoplastic Agents/chemical synthesis , Hydroquinones/chemistry , Phosphorous Acids/chemistry , A549 Cells , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Drug Screening Assays, Antitumor , Fluorouracil/toxicity , HeLa Cells , Humans , MCF-7 Cells , Microscopy, Fluorescence , Phosphorous Acids/chemical synthesis , Phosphorous Acids/pharmacology , S Phase Cell Cycle Checkpoints/drug effects
17.
Chem Biol Drug Des ; 86(6): 1339-50, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26041467

ABSTRACT

A series of (E,Z)-1-(dihydrobenzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propen-1-ones (C1-C35) were designed and synthesized, and the structures of compounds (Z)-C27 and (Z)-C29 were confirmed by single-crystal X-ray diffraction. The antitumor activities of these novel compounds against cervical cancer (HeLa), lung cancer (A549), and breast cancer (MCF-7) cell lines were evaluated in vitro. Majority of the title compounds exhibited strong antitumor activities and were much more promising than the positive control Taxol, which were also accompanied by lower cytotoxicity to normal cells. In particular, compounds (E,Z)-C24 exhibited the most consistent potent activities against three neoplastic cells with IC50 values ranging from 3.2 to 7.1 µm. Further researches demonstrated that compounds (E,Z)-C24 could induce cell apoptosis and arrest cell cycle at the G2/M and S phases. Meanwhile, the structure-activity relationship between the configurations and cytotoxicity of the compounds was also investigated.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Benzofurans/chemical synthesis , Benzofurans/pharmacology , Drug Design , Neoplasms/drug therapy , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Benzofurans/chemistry , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Cycle/drug effects , Cell Line, Tumor , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Female , HEK293 Cells , HeLa Cells , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , MCF-7 Cells , Neoplasms/pathology , Structure-Activity Relationship , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathology
18.
Arch Pharm (Weinheim) ; 347(2): 89-95, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24243443

ABSTRACT

Based on the positive effects of COX-2 inhibitors on depressive symptoms and the desirable physicochemical and biological properties of the morpholine group, a series of novel 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides were designed, synthesized, and tested for their COX-2 inhibitory and serotonin reuptake inhibitory activities in vitro. The structure-activity relationships of the 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides as dual COX-2 and serotonin reuptake inhibitors were determined and discussed in detail. The biological assays indicated that five of the compounds possess good COX-2 selectivity (selectivity index COX-1/COX-2 42.8-158.1). The compound 2-[2-(4-benzyloxyphenyl)morpholino]ethyl 2-(4-iso-butylphenyl)-propanoate hydrochloride (1k) shows better COX-2 inhibitory activity (IC50 = 0.78 µM) than ibuprofen (IC50 = 7.6 µM), and it simultaneously possesses favorable serotonin reuptake inhibitory activity.


Subject(s)
Cyclooxygenase 2 Inhibitors/chemical synthesis , Cyclooxygenase 2 Inhibitors/pharmacology , Esters/chemical synthesis , Esters/pharmacology , Ibuprofen/chemical synthesis , Ibuprofen/pharmacology , Selective Serotonin Reuptake Inhibitors/chemical synthesis , Selective Serotonin Reuptake Inhibitors/pharmacology , Animals , Caco-2 Cells , Cyclooxygenase 2/metabolism , Dose-Response Relationship, Drug , Drug Design , Humans , Ibuprofen/analogs & derivatives , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/enzymology , Mice , Molecular Structure , RNA-Binding Proteins/antagonists & inhibitors , RNA-Binding Proteins/metabolism , Rats , Serotonin Plasma Membrane Transport Proteins/drug effects , Serotonin Plasma Membrane Transport Proteins/metabolism , Structure-Activity Relationship
19.
Arch Pharm (Weinheim) ; 346(9): 635-44, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23926081

ABSTRACT

With a convenient and economical method, two series of 1,3-thiazine derivatives 1 and 2 were synthesized, and their neuraminidase (NA) inhibitory activities were evaluated. The pharmacological results showed that most of the compounds have potent NA inhibitory activity. Especially, 1g exhibited the best activity against influenza virus A (H1N1) NA (IC50=29.06 µg/mL), and its crystal structure was determined by single-crystal X-ray diffraction. The preliminary biological assay indicated that 1,3-thiazine could be used as a core structure to design novel influenza NA inhibitors.


Subject(s)
Antiviral Agents/pharmacology , Influenza A Virus, H1N1 Subtype/drug effects , Neuraminidase/antagonists & inhibitors , Thiazines/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Crystallography, X-Ray , Drug Design , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Inhibitory Concentration 50 , Structure-Activity Relationship , Thiazines/chemical synthesis , Thiazines/chemistry
20.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 2): o338, 2011 Jan 12.
Article in English | MEDLINE | ID: mdl-21523021

ABSTRACT

The title compound, C(21)H(22)O(5), crystallizes with three mol-ecules in the asymmetric unit. In one mol-ecule, two methyl groups are disordered over two positions with a site occupation factor of 0.72 (2) for the major occupancy site. The benzene rings make dihedral angles of 35.3 (6), 29.7 (6) and 40.6 (7)° in the three molecules.

SELECTION OF CITATIONS
SEARCH DETAIL
...