- Synthesis, antimicrobial and antioxidant evaluation with in silico studies of new thiazole Schiff base derivatives
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A series of nineteen thiazole Schiff base derivatives 2a-2s were synthesized (Scheme 1) and elucidated by spectral analyses (IR, 1H NMR and HRMS). The evaluation of their antimicrobial activities against two gram-positive, two gram-negative, an
- Ahmed, Junaid Uddin,Al-Macktuf, Abdullah,Haque, Md. Aminul,Islam, Md. Din,Nishino, Hiroshi,Rahman, Mohammad Mostafizur,Shah, Md. Shahazada
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- Synthesis, characterization, alkaline phosphatase inhibition assay and molecular modeling studies of 1-benzylidene-2-(4-tert- butylthiazol-2-yl) hydrazines
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Alkaline phosphatases are homodimeric protein enzymes which removes phosphates from several types of molecules. These catalyze the hydrolysis of monoesters in phosphoric acid which in turn catalyze a transphosphorylation reaction. Thiazoles are a privileged class of heterocyclic compounds which may potentially serve as effective phosphatase inhibitors. In this regard, the present research paper reports the facile synthesis and characterization of substituted 1-benzylidene-2-(4-tert-butylthiazol-2-yl) hydrazines with excellent yields. The synthesized compounds were tested for inhibitory potential against alkaline phosphatases. The compound 1-(4-Hydroxy, 3-methoxybenzylidene)-2-(4-tert-butylthiazol-2-yl) hydrazine (5e) was found to be the most potent inhibitor of human tissue non-alkaline phosphatase in this group of molecules with an IC50 value of 1.09 ± 0.18 μM. The compound 1-(3,4-dimethoxybenzylidene)-2-(4-tert-butylthiazol-2-yl) hydrazine (5d) exhibited selectivity and potency for human intestinal alkaline phosphatase with an IC50 value of 0.71 ± 0.02 μM. In addition, structure activity relationship and molecular docking studies were performed to evaluate their binding modes with the target site of alkaline phosphatase. The docking analysis revealed that the most active inhibitors showed the important interactions within the binding pockets of human intestinal alkaline phosphatase and human tissue non-alkaline phosphatase and may be responsible for the inhibitory activity of the compound towards the enzymes. Therefore, the screened thiazole derivatives provided an outstanding platform for further development of alkaline phosphatase inhibitors.
- Aziz, Hamid,Mahmood, Abid,Zaib, Sumera,Saeed, Aamer,El-Seedi, Hesham R.,Pelletier, Julie,Sévigny, Jean,Iqbal, Jamshed
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p. 6140 - 6153
(2020/08/14)
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- Design, synthesis and biological assessment of new selective COX-2 inhibitors including methyl sulfonyl moiety
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Nonsteroidal anti-inflammatory drugs (NSAIDs) cause peptic lesions in the gastrointestinal mucosa by inhibiting the cyclooxygenase-1 (COX-1) enzyme. Selective COX-2 inhibition causes decreased side effects over current NSAIDs. Therefore, the studies about selective inhibition of COX-2 enzyme are very important for new drug development. The design, synthesis and biological activity evaluation of novel derivatives bearing thiazolylhydrazine-methyl sulfonyl moiety as selective COX-2 inhibitors were aimed in this paper. The structures of synthesized compounds were assigned using different spectroscopic techniques such as 1H NMR, 13C NMR and HRMS. In addition, the estimation of ADME parameters for all compounds was carried out using in silico process. The evaluation of in vitro COX-1/COX-2 enzyme inhibition was applied according to the fluorometric method. According to the enzyme inhibition results, synthesized compounds showed the selectivity against COX-2 enzyme inhibition as expected. Compounds 3a, 3e, 3f, 3g, 3i and 3j demonstrated significant COX-2 inhibition potencies. Among them, compound 3a was found to be the most effective derivative with an IC50 value of 0.140 ± 0.006 μM. Moreover, it was seen that compound 3a displayed a more potent inhibition profile at least 12-fold than nimesulide (IC50 = 1.684 ± 0.079 μM), while it showed inhibitory activity at a similar rate of celecoxib (IC50 = 0.132 ± 0.005 μM). Molecular modelling studies aided in the understanding of the interaction modes between this compound and COX-2 enzyme. It was found that compound 3a had a significant binding property. In addition, the selectivity of obtained derivatives on COX-2 enzyme could be explained and discussed by molecular docking studies.
- Sa?l?k, Begüm Nurpelin,Osmaniye, Derya,Levent, Serkan,?evik, Ulviye Acar,?avu?o?lu, Betül Kaya,?zkay, Yusuf,Kaplanc?kl?, Zafer As?m
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- Assessment of Thiosemicarbazone-Containing Compounds as Potential Antileukemia Agents against P-gp Overexpressing Drug Resistant K562/A02 Cells
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P-Glycoprotein (P-gp) overexpression is considered to be the leading cause of multidrug resistance (MDR) and failure of chemotherapy for leukemia. In this study, seventeen thiosemicarbazone-containing compounds were prepared and evaluated as potential ant
- Gu, Xiaoke,Guan, Mingyu,Jiang, Chunyu,Song, Qinghua,Li, Xin,Sun, Nan,Chen, Jing,Qiu, Jingying
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- Discovery of new coumarin-based lead with potential anticancer, cdk4 inhibition and selective radiotheranostic effect: Synthesis, 2d & 3d qsar, molecular dynamics, in vitro cytotoxicity, radioiodination, and biodistribution studies
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Novel 6-bromo-coumarin-ethylidene-hydrazonyl-thiazolyl and 6-bromo-coumarin-thiazolylbased derivatives were synthesized. A quantitative structure activity relationship (QSAR) model with high predictive power r2 = 0.92, and RMSE = 0.44 predicted five compounds; 2b, 3b, 5a, 9a and 9i to have potential anticancer activities. Compound 2b achieved the best ?G of –15.34 kcal/mol with an affinity of 40.05 pki. In a molecular dynamic study 2b showed an equilibrium at 0.8 ? after 3.5 ns, while flavopiridol did so at 0.5 ? after the same time (3.5 ns). 2b showed an IC50 of 0.0136 μM, 0.015 μM, and 0.054 μM against MCF-7, A-549, and CHO-K1 cell lines, respectively. The CDK4 enzyme assay revealed the significant CDK4 inhibitory activity of compound 2b with IC50 of 0.036 μM. The selectivity of the newly discovered lead compound 2b toward localization in tumor cells was confirmed by a radioiodination biological assay that was done via electrophilic substitution reaction utilizing the oxidative effect of chloramine-t.131 I-2b showed good in vitro stability up to 4 h. In solid tumor bearing mice, the values of tumor uptake reached a height of 5.97 ± 0.82%ID/g at 60 min p.i.131 I-2b can be considered as a selective radiotheranostic agent for solid tumors with promising anticancer activity.
- Sarhan, Mona O.,Abd El-Karim, Somaia S.,Anwar, Manal M.,Gouda, Raghda H.,Zaghary, Wafaa A.,Khedr, Mohammed A.
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- In vitro evaluation of new 4-thiazolidinones on invasion and growth of Toxoplasma gondii
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Treatments for toxoplasmosis such as pyrimethamine have shown numerous side effects. It has been reported that the likelihood of relapse associated with pyrimethamine-based therapy in patients with HIV and toxoplasmic encephalitis (TE) can have significant implications, even for patients who often develop new lesions in areas of the brain previously free of infection. This led us to research for new agents against Toxoplasma gondii. Recent findings have shown the potent biological activity of 4-thiazolidinones. We proposed to design and synthesize a new series of 2-hydrazono-4-thiazolidinones derivatives to evaluate the in vitro growth inhibition effect on T. gondii. The growth rates of T. gondii tachyzoites in Human Foreskin Fibroblast (HFF) cell culture were identified by two in vitro methodologies. The first one was by fluorescence in which green fluorescent RH parasites and cherry-red fluorescent ME49 parasites were used. The second one was a colorimetric methodology using β-Gal parasites of the RH strain constitutively expressing the enzyme beta-galactosidase. The 4-thiazolidinone derivatives 1B, 2B and 3B showed growth inhibition at the same level of Pyrimethamine. These compounds showed IC50 values of 1B (0.468–0.952 μM), 2B (0.204–0.349 μM) and 3B (0.661–1.015 μM) against T. gondii. As a measure of cytotoxicity the compounds showed a TD50 values of: 1B (60 μM), 2B (206 μM) and 3B (125 μM). The in vitro assays and molecular modeling results suggest that these compounds could act as possible inhibitors of the Calcium-Dependent Protein Kinase 1 of T. gondii. Further, our results support the fact that of combining appropriate detection technologies, combinatorial chemistry and computational biology is a good strategy for efficient drug discovery. These compounds merit in vivo analysis for anti-parasitic drug detection.
- Molina, Diego A.,Ramos, Gerardo A.,Zamora-Vélez, Alejandro,Gallego-López, Gina M.,Rocha-Roa, Cristian,Gómez-Marin, Jorge Enrique,Cortes, Edwar
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p. 129 - 139
(2021/06/15)
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- Design, synthesis, biological evaluation, QSAR analysis and molecular modelling of new thiazol-benzimidazoles as EGFR inhibitors
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Heterocyclic rings such as thiazole and benzimidazole are considered as privileged structures, since they constitute several FDA-approved drugs for cancer treatment. In this work, a new set of 2-(2-(substituted) hydrazinyl)-4-(1-methyl-1H-benzo[d]imidazol-2-yl) thiazoles 4a-q were designed as epidermal growth factor receptor (EGFR) inhibitors and synthesized using concise synthetic methods. The new target compounds have been evaluated in vitro for their suppression activity against EGFR TK. Compounds 4n, 4h, 4i, 4a and 4d exhibited significant potency in comparison with erlotinib which served as a reference drug (IC50, 71.67–152.59 nM; IC50 erlotinib, 152.59 nM). Furthermore, MTT assay revealed that compounds 4j, 4a, 4f, 4h, 4n produced the most promising cytotoxic potency against the human breast cancer cell line (MCF-7) (IC50; 5.96–11.91 μM; IC50 erlotinib; 4.15 μM). Compound 4a showed promising activity as EGFR TK inhibitor as well as anti-breast cancer agent. In addition, 4a induced apoptotic effect and cell cycle arrest at G2/M phase preventing the mitotic cycle in MCF-7 cells. Moreover, 4a upregulated the oncogenic parameters; caspase-3, p53, Bax/Bcl-2 as well as it inhibited the level of PARP-1 enzyme. QSAR study was carried out for the new derivatives and it revealed the goodness of the models. Furthermore, molecular docking studies represented the binding modes of the promising compounds in the active pocket of EGFR.
- Abd El-Karim, Somaia S.,Ahmed, Nesreen S.,Anwar, Manal M.,El-Hallouty, Salwa M.,Srour, Aladdin M.
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supporting information
(2020/08/06)
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- Design, synthesis, and structure–Activity relationships of thiazole analogs as anticholinesterase agents for alzheimer’s disease
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Dementia is a neurological condition commonly correlated with Alzheimer’s disease (AD), and it is seen with many other central nervous system (CNS) disorders. The restricted number of medications is not appropriate to offer enough relief to enhance the quality of life of patients suffering from this symptom; thus, all therapeutic choices should be carefully assessed. In this study, new thiazolylhydrazone derivatives (2a–2l) were designed and synthesized based on the cholinergic hypothesis. Their chemical structures were confirmed by 1H NMR, 13C NMR, and HRMS spectrometric techniques. The ADME (absorption, distribution, metabolism, elimination) parameters of the synthesized compounds were predicted by using QikProp 4.8 software. It was concluded that all compounds presented satisfactory drug-like characteristics. Furthermore, their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro were also tested by modified the Ellman spectrophotometric method. According to the results, all compounds showed a weak inhibitory effect on BChE. On the other hand, most of the compounds (2a, 2b, 2d, 2e, 2g, 2i, and 2j) had a certain AChE inhibitory activity, and the IC50 values of them were calculated as 0.063 ± 0.003, 0.056 ± 0.002, 0.147 ± 0.006, 0.040 ± 0.001, 0.031 ± 0.001, 0.028 ± 0.001, and 0.138 ± 0.005 μM, respectively. Among these derivatives, compound 2i was found to be the most active agent in the series with an IC50 value of 0.028 ± 0.001 μM, which indicated an inhibition profile at a similar rate as the reference drug, donepezil. The potential binding modes of compounds 2a, 2b, 2e, 2g, and 2i with AChE were investigated and compared with each other by the molecular docking studies. The results showed that these compounds were strongly bound up with the AChE enzyme active site with the optimal conformations.
- ?avu?og?lu, Betül Kaya,?evik, Ulviye Acar,?zkay, Yusuf,Kaplanc?kl?, Zafer As?m,Levent, Serkan,Osmaniye, Derya,Sa?l?k, Begüm Nurpelin
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- Synthesis and antiviral activity of novel 1,3,4-thiadiazole inhibitors of DDX3x
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The human ATPase/RNA helicase X-linked DEAD-box polypeptide 3 (DDX3X) emerged as a novel therapeutic target in the fight against both infectious diseases and cancer. Herein, a new family of DDX3X inhibitors was designed, synthesized, and tested for its inhibitory action on the ATPase activity of the enzyme. The potential use of the most promising derivatives it has been investigated by evaluating their anti-HIV-1 effects, revealing inhibitory activities in the low micromolar range. A preliminary ADME analysis demonstrated high metabolic stability and good aqueous solubility. The promising biological profile, together with the suitable in vitro pharmacokinetic properties, make these novel compounds a very good starting point for further development.
- Brai, Annalaura,Ronzini, Stefania,Riva, Valentina,Botta, Lorenzo,Zamperini, Claudio,Borgini, Matteo,Trivisani, Claudia Immacolata,Garbelli, Anna,Pennisi, Carla,Boccuto, Adele,Saladini, Francesco,Zazzi, Maurizio,Maga, Giovanni,Botta, Maurizio
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- Acetic acid mediated regioselective synthesis of 2,4,5-trisubstituted thiazoles by a domino multicomponent reaction
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Acetic acid mediated regioselective synthesis of novel 2,4,5-trisubstituted thiazole derivatives has been reported by a domino reaction of thiosemicarbazide and aldehydes/ketones/isatin, to generate thiosemicarbazones (in situ) followed by addition of arylglyoxal and active methylene/activated C-H acids/pyrazole/indole in ethanol at 80 °C. The products are obtained in high yields by a simple work up. Metal free, short reaction time and high yields are some merits of this methodology.
- Saroha, Mohit,Khurana, Jitender M.
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p. 8644 - 8650
(2019/06/14)
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- Synthesis, characterization and biological evaluation of some novel fluoroquinolones
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Different derivatives of fluoroquinolones were synthesized by combining it with different thiadiazoles. The synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance and mass spectral data. The compounds were screened for their antibacterial and antifungal activity. Ciprofloxacin derivatives with thiadiazoles 7c showed good antibacterial as well as antifungal activities, whereas 13c and 13e showed antibacterial and antifungal activity respectively. Sparfloxacin derivative 8c showed both antibacterial and antifungal activity. Sparfloxacin derivatives 14b and 14e showed antibacterial and antifungal activity respectively.
- Pandit, Neelanjana,Shah, Kamal,Agrawal, Neetu,Upmanyu, Neeraj,Shrivastava, Sushant K.,Mishra, Pradeep
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p. 843 - 851
(2016/04/20)
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- Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases rhodesain, cruzain, and Schistosoma mansoni cathepsin B1
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The pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, and Schistosoma mansoni CB1 (SmCB1), the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei, and S. mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC50s) of ≤10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC50 = 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluated in vitro against the parasites T. cruzi, T. brucei, and S. mansoni, revealing active compounds among this series.
- Fonseca, Nayara Cristina,Da Cruz, Luana Faria,Da Silva Villela, Filipe,Do Nascimento Pereira, Glaécia Aparecida,De Siqueira-Neto, Jair Lage,Kellar, Danielle,Suzuki, Brian M.,Ray, Debalina,De Souza, Thiago Belarmino,Alves, Ricardo José,Júnior, Policarpo Ademar Sales,Romanha, Alvaro José,Murta, Silvane Maria Fonseca,McKerrow, James H.,Caffrey, Conor R.,De Oliveira, Renata Barbosa,Ferreira, Rafaela Salgado
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p. 2666 - 2677
(2015/06/23)
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- Thiazole compounds with activity against Cryptococcus gattii and Cryptococcus neoformans in vitro
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Human cryptococcosis can occur as a primary or opportunistic infection and develop as an acute, subacute, or chronic, systemic infection involving different host organs. We evaluated the antifungal activity of thirteen compounds against Cryptococcus gattii and Cryptococcus neoformans in vitro, by assessing the toxicity of the compounds showing the greatest antifungal activity in VERO cells and murine macrophages. From these results, four compounds were considered promising for further studies because they displayed low cytotoxicity and significant antifungal activity. The heterocyclic compounds 1b, 1c, 1d, and 1m have antifungal activity levels between that of amphotericin B and fluconazole in vitro. The death curve of Cryptococcus spp. treated with these four compounds was similar to the curve obtained for amphotericin B, in that we observed a significant reduction in cell viability within the first 24 h of treatment. Additionally, we found that there was no effect when these compounds were combined with amphotericin and fluconazole, except for 1c, which antagonized the effect of amphotericin B against C. gattii, also reflected in the reduction of the post-antifungal effect (PAFE); however, this interaction did not alter the ergosterol content. The results shown in this paper reveal the discovery of novel thiazole compounds, which are easy to synthesize, and with potentially exhibit antifungal activity, and display low cytotoxicity in normal mammalian cells. These compounds can be used as prototypes for the design of new antifungal drugs against C. gattii and C. neoformans.
- Pereira de Sá, Nívea,Lino, Cleudiomar Inácio,Fonseca, Nayara Cristina,Borelli, Beatriz Martins,Ramos, Jonas Pereira,Souza-Fagundes, Elaine Maria,Rosa, Carlos Augusto,Santos, Daniel Assis,Barbosa De Oliveira, Renata,Johann, Susana
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p. 233 - 242
(2015/08/24)
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- Synthesis, molecular docking, acetylcholinesterase and butyrylcholinesterase inhibitory potential of thiazole analogs as new inhibitors for Alzheimer disease
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A series of thirty (30) thiazole analogs were prepared, characterized by 1H NMR, 13C NMR and EI-MS and evaluated for Acetylcholinesterase and butyrylcholinesterase inhibitory potential. All analogs exhibited varied butyrylcholinester
- Rahim, Fazal,Javed, Muhammad Tariq,Ullah, Hayat,Wadood, Abdul,Taha, Muhammad,Ashraf, Muhammad,Qurat-Ul-Ain,Khan, Muhammad Anas,Khan, Fahad,Mirza, Salma,Khan, Khalid M.
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p. 106 - 116
(2015/09/02)
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- Synthesis, antibacterial, antioxidant activity and QSAR studies of novel 2-arylidenehydrazinyl-4-arylthiazole analogues
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A novel series of 2-arylidenehydrazinyl-4-arylthiazole analogues (3a-p) was designed and synthesized in excellent yields using a rapid, simple, efficient methodology. Sixteen novel compounds were screened for in vitro antimicrobial activities against eleven bacteria, namely, Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, Bacillus subtilis, Klebsiella pneumonia, Citrobacter freundii, Cronobacter sakazakii, Salmonella enteritidis, Escherichia coli, Yersinia pestis, and Pseudomonas aeruginosa. All 16 compounds showed significant anti-bacterial activities against both Gram-positive and Gram-negative bacteria. In particular, compound 3g showed potent inhibition of E. coli and K. pneumonia, compound 3i inhibited E. faecalis, compound 3n S. tythi and E. faecalis, and compound 3c E. coli and C. sakazakii. In fact, our results indicate that most of the compounds synthesized exhibit strong antibacterial activity. The qualitative structure-antibacterial activity relationships (QSAR) were studied using the physicochemical and quantum-chemical parameters of the ab initio Hartree-Fock model at the RHF/6-31G level of theory. A good qualitative correlation between predicted physicochemical parameters (log P and polar surface area (PSA)) and antibacterial activity has been found. The synthesized compounds were also evaluated for antioxidant activity. Compounds 3j, 3a and 3i exhibited the greatest antioxidant activity, with IC50 values of 0.66, 0.81, and 1.08 μM, respectively, which were comparable to that of ascorbic acid (IC50 0.87 μM). The promising antibacterial and antioxidant activities of some of these synthesized 2-arylidenehydrazinyl-4-arylthiazole derivatives, together with the results of quantum-chemical studies, could be helpful for the development of drugs to combat diseases caused by microorganisms and oxidative stress.
- Alam, Mohammad Sayed,Ahmed, Junaid Uddin,Lee, Dong-Ung
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p. 1259 - 1268
(2015/02/19)
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- In vitro and in silico antimalarial activity of 2-(2-hydrazinyl)thiazole derivatives
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A series of 2-(2-hydrazinyl)thiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were synthesized, characterized and evaluated their inhibitory potentials against plasmodium falciparum, NF54, by in vitro blood stage assay. The compounds, ethyl-4-methyl-2-[(E)-2-[1-(pyridin-2- yl)ethylidene]hydrazin-1-yl]-1,3-thiazole-5-carboxylate, 4d, and 1-{4-methyl-2-[(E)-2-[1-(pyridin-2-yl)ethylidene]hydrazin-1-yl]-1, 3-thiazol-5-yl}ethan-1-one, 5d showed significant antimalarial activity with IC50 values of 0.725 μM and 0.648 μM respectively. To understand the mechanism, the binding interactions between 2-(2-hydrazinyl) thiazole derivatives and trans-2-enoyl acyl carrier protein reductase of P. falciparum were studied through docking studies. The half maximal inhibitory concentration (IC50) through docking studies for the compounds, 4d and 5d were found to be 22.88 μM and 631.84 μM respectively.
- Makam, Parameshwar,Thakur, Prasoon Kumar,Kannan, Tharanikkarasu
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p. 138 - 145
(2014/01/06)
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- Synthesis and characterization of zinc(II) complexes with 3,4-dimethoxybenzaldehyde thiosemicarbazone: The crystal structure of [Zn(34-MBTSC) 2Cl 2]
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The synthesis and characterization of three zinc(II) complexes [Zn(34-MBTSC)2Cl2] (1), [Zn(34-MBTSC)2Br 2] (2), and [Zn(34-MBTSC)2I2] (3) of 3,4-dimethoxybenzaldehyde thiosemicarbazone (34-
- Khalaji, Aliakbar Dehno,Grivani, Gholamhossein,Rezaei, Morteza,Fejfarova, Karla,Dusek, Michal
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p. 1119 - 1126
(2013/09/02)
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- Synthesis and biological assessment of novel 2-thiazolylhydrazones and computational analysis of their recognition by monoamine oxidase B
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Monoamine oxidase B (MAO-B) is a promising target for the treatment of neurodegenerative disorders. We report the synthesis and the biological evaluation of halogenated derivatives of 1-aryliden-2-(4-phenylthiazol-2-yl) hydrazines. The fluorinated series shows interesting activity and great selectivity toward the human recombinant MAO-B isoform expressed in baculovirus infected BTI insect cells. The multiple crystal structures alignment of the enzyme highlighted pronounced induced fit (IF) adaptations with respect to bound ligands. Therefore, IF docking (IFD) experiments and molecular dynamic (MD) simulations were carried out to reveal the putative binding mode and to explain the experimentally observed differences in the activity of 1-(aryliden-2-(4-(4- chlorophenyl)thiazol-2-yl)hydrazines. The importance of water molecules within the binding site was also investigated. These are known to play an important role in the binding site cavity and to mediate protein-ligand interactions. Detailed analyses of the trajectories provide insights on the chemical features required for the activity of this scaffold. In particular it was highlighted the importance of fluorine atom interacting with the water close to the cofactor and the influence of steric bulkiness of substituents in the arylidene moiety. Free energy perturbation (FEP) analysis confirmed experimental data. The information we deduced will help to develop novel high-affinity MAO-B inhibitors.
- Distinto, Simona,Yá?ez, Matilde,Alcaro, Stefano,Cardia, M. Cristina,Gaspari, Marco,Sanna, M. Luisa,Meleddu, Rita,Ortuso, Francesco,Kirchmair, Johannes,Markt, Patrick,Bolasco, Adriana,Wolber, Gerhard,Secci, Daniela,MacCioni, Elias
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scheme or table
p. 284 - 295
(2012/04/10)
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- Synthesis, anti-bacterial and anti-fungal activities of some novel Schiff bases containing 2,4-disubstituted thiazole ring
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A series of arylidene-2-(4-(4-methoxy/bromophenyl) thiazol-2-yl) hydrazines (4a-z) and 1-(4-(4-methoxy/bromophenyl) thiazol-2-yl)-2-cyclohexylidene/cyclopentylidene hydrazines (5a-b/6a-b) were synthesized, characterized and screened for their antimicrobial activities. The structures of synthesized compounds were established by spectroscopic (FT-IR, 1H NMR, 13C NMR, Mass) and elemental analyses. Both the anti-bacterial and anti-fungal activities with MIC values of compounds were evaluated. The results of anti-bacterial screening reveal that among all the compounds screened eight compounds showed moderate to good anti-bacterial activity while ten of the newly synthesized compounds displayed good to excellent anti-fungal activity. Among the tested compounds, the most effective compounds with MIC value in the range of 6.25-25 μg/ml are 4a, 4n, 4z, 5a, 5b, 6a and 6b against three fungal strains viz. Candida albicans, Cryptococcus neoformans and Aspergillus flavus.
- Bharti,Nath,Tilak,Singh
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experimental part
p. 651 - 660
(2010/04/02)
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- Selective inhibitory activity against MAO and molecular modeling studies of 2-thiazolylhydrazone derivatives
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A series of 2-thiazolylhydrazone derivatives have been investigated for the ability to inhibit the activity of the A and B isoforms of monoamine oxidase (MAO) selectively. All of the compounds showed high activity against both the MAO-A and the MAO-B isoforms with pKi values ranging between 5.92 and 8.14 for the MAO-A and between 4.69 and 9.09 for the MAO-B isoforms. Both the MAO-A and the MAO-B isoforms, deposited in the Protein Data Bank as model 2BXR and 1GOS, respectively, were considered in a computational study performed with docking techniques on the most active and MAO-B-selective inhibitor, 18.
- Chimenti, Franco,Maccioni, Elias,Secci, Daniela,Bolasco, Adriana,Chimenti, Paola,Granese, Arianna,Befani, Olivia,Turini, Paola,Alcaro, Stefano,Ortuso, Francesco,Cardia, Maria C.,Distinto, Simona
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p. 707 - 712
(2007/10/03)
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