Showing papers in "Archiv Der Pharmazie in 2013"
TL;DR: A series of sulfonamides synthesized from dopamine derivatives showed around 75–85% inhibition on linoleic acid peroxidation and the inhibition effects of the synthesized compounds on acetylcholinesterase (AChE) activity were evaluated.
Abstract: A series of sulfonamides were synthesized from dopamine derivatives. The reactions of amines with methanesulfonyl chloride followed by O-demethylation with BBr3 afforded phenolic sulfonamides. The antioxidant activities of the synthesized phenolic sulfonamides were investigated by thiocyanate method, 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS(center dot+)), 1,1-diphenyl-2-picryl-hydrazyl (DPPH center dot), N,N-dimethyl-p-phenylenediamine (DMPD center dot+), and superoxide anion (O-2(center dot-)) radical scavenging, reducing power, and ferrous ion (Fe2+) chelating assays. Sulfonamides 13-16 showed around 75-85% inhibition on linoleic acid peroxidation. On the other hand, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), -tocopherol, and trolox indicated an inhibition of 90.0%, 85.73%, 73.33%, and 85.73% on peroxidation, respectively, in the same system at the same concentration (10 mu g/mL). Also, the inhibition effects of the synthesized compounds on acetylcholinesterase (AChE) activity were evaluated. AChE was effectively inhibited by sulfanomides 13-16, with K-i values in the range of 33.04 +/- 4.3 to 131.68 +/- 8.8nM.
145 citations
TL;DR: The current review article summarizes and discusses endeavours towards the developments in the burgeoning field of urease inhibition in medicinal chemistry, with an emphasis on the insights that have been gleaned into the structural features that contribute to high and promising levels of anti‐urease activity.
Abstract: Ureases have emerged as significant virulence factors implicated in the pathogenesis of many clinical conditions such as pyelonephritis, hepatic coma, peptic ulceration, and the formation of injection-induced urinary stones and stomach cancer They have also been identified as important targets in research both for human and animal health, as well as in agriculture Strategies based on urease inhibition are the main treatment of diseases caused by urease-producing bacteria So, in the present context, a diverse library of chemical structures is known to possess remarkable inhibitory activities against urease enzymes The current review article summarizes and discusses endeavours towards the developments in the burgeoning field of urease inhibition in medicinal chemistry, with an emphasis on the insights that have been gleaned into the structural features that contribute to high and promising levels of anti-urease activity
71 citations
TL;DR: A series of 2‐aryl/heteroaryl‐4‐quinolones (aza analogs of flavones) was rationally designed, synthesized and evaluated for in vitro XO inhibitory activity and some notions about structure–activity relationships are presented.
Abstract: In an attempt to develop non-purine-based xanthine oxidase (XO) inhibitors, keeping in view the complications reported with the use of purine-based XO inhibitors, the flavone framework (a class possessing XO inhibitory potential) was used as lead structure for further optimization. By means of structure-based classical bioisosterism, quinolone was used as an isoster for chromone (a bicyclic unit present in flavones), owing to the bioactive potential and drug-like properties of quinolones. This type of replacement does not alter the shape and structural features required for XO inhibition, and also provides some additional interaction sites, without the loss of hydrogen bonding and hydrophobic and arene-arene interactions. In the present study, a series of 2-aryl/heteroaryl-4-quinolones (aza analogs of flavones) was rationally designed, synthesized and evaluated for in vitro XO inhibitory activity. Some notions about structure-activity relationships are presented indicating the influence of the nature of the 2-aryl ring on the inhibitory activity. Important interactions of the most active compound 3l (IC(50) = 6.24 µM) with the amino acid residues of the active site of XO were figured out by molecular modeling.
62 citations
TL;DR: 2‐(1,8‐Diethyl‐1,3, 4,9‐tetrahydropyrano[3,4‐b]indole‐1‐yl)acetic acid[(4‐chlorophenyl)methylene]hydrazide 9 demonstrated the most marked effect on the prostate cancer cell line PC‐3, with 58.24% growth inhibition at 10−5 M (10 µM).
Abstract: Etodolac hydrazide and a novel series of etodolac hydrazide-hydrazones 3-15 and etodolac 4-thiazolidinones 16-26 were synthesized in this study. The structures of the new compounds were determined by spectral (FT-IR, (1)H NMR, (13)C NMR, HREI-MS) methods. Some selected compounds were determined at one dose toward the full panel of 60 human cancer cell lines by the National Cancer Institute (NCI, Bethesda, USA). 2-(1,8-Diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-yl)acetic acid[(4-chlorophenyl)methylene]hydrazide 9 demonstrated the most marked effect on the prostate cancer cell line PC-3, with 58.24% growth inhibition at 10(-5) M (10 µM). Using the MTT colorimetric method, compound 9 was evaluated in vitro against the prostate cell line PC-3 and the rat fibroblast cell line L-929, for cell viability and growth inhibition at different doses. Compound 9 exhibited anticancer activity with an IC(50) value of 54 µM (22.842 µg/mL) against the PC-3 cells and did not display any cytotoxicity toward the L-929 rat fibroblasts, compared to etodolac. In addition, this compound was evaluated for caspase-3 and Bcl-2 activation in the apoptosis pathway, which plays a key role in the treatment of cancer.
46 citations
TL;DR: A facile one‐pot four‐component reaction was utilized to construct 2‐oxo‐1,2‐dihydropyridine‐3‐carbonitrile as a scaffold for the synthesis of many fused heterocyclic systems, namely, furopyridine, pyridothiadiazepinthione, and pyrIDotriazine.
Abstract: A facile one-pot four-component reaction was utilized to construct 2-oxo-1,2-dihydropyridine-3-carbonitrile as a scaffold for the synthesis of many fused heterocyclic systems, namely, furopyridine, pyridothiadiazepinthione, and pyridotriazine, as well as non-fused heterocyclic systems such as phthalazin-2(1H)-ylnicotinonitrile, pyridin-2-yl-1H-pyrazole, and pyrazol-1-ylnicotino-nitrile,1-(3-cyanopyridin-2-yl)-1H-pyrazole. The new compounds were evaluated as antimicrobial and antiviral agents.
43 citations
TL;DR: The compounds showed strong inhibitory activity against hCA I, being more effective as compared to the clinically used AZA, but rather less activity againsthCA II, while the structurally related compound 14 was tested in order to understand the structure–activity relationship.
Abstract: Here, we provide an alternative synthesis of the natural bromophenol 3,4-dibromo-5-(2,3-dibromo-4,5-dihydroxybenzyl)-6-(ethoxymethyl)benzene-1,2-diol (3) and the first synthesis of (4,5-dihydroxy-2-methylphenyl)(3,4-dihydroxyphenyl)methanone (18) and its brominated derivatives 19-21. The compounds were characterized and tested against the two most studied members of the pH regulatory enzyme family, carbonic anhydrase (CA). The inhibitory potencies of the novel compounds and two natural bromophenols 2, 3 were analyzed at the human isoforms hCA I and hCA II as targets and the KI values were calculated. The KI values of the novel compounds were measured in the range of 13.7-32.7 mM for the hCA I isozyme and 0.65-1.26 mM for the hCA II isozyme. The structurally related compound 14 was also tested in order to understand the structure–activity relationship, and the clinically used sulfonamide acetazolamide (AZA)was tested for comparison reasons. All of the compounds exhibited competitive inhibition with 4-nitrophenylacetate as substrate. The compounds showed strong inhibitory activity against hCA I, being more effective as compared to the clinically used AZA (KI: 36.2 mM), but rather less activity against hCA II.
37 citations
TL;DR: The potencies of compound 8h against seizures induced by pentylenetetrazole and thiosemicarbazide were established, with the results suggesting that the GABAergic system‐mediated mechanisms might be involved in its anticonvulsant activity.
Abstract: In the present study we describe the syntheses and anticonvulsant activity evaluation of 5-phenyl-[1,2,4]triazolo[4,3-c]quinazolin-3-amine derivatives. Their anticonvulsant activity and neurotoxicity were evaluated by the maximal electroshock seizure test (MES) and the rotarod test, respectively. The majority of the compounds prepared were effective in the MES screens at a dose level of 100 mg/kg. Of these compounds, the most promising was compound 8h, which showed an ED(50) value of 27.4 mg/kg and a protective index (PI) value of 5.8. These values were superior to those provided by valproate (ED(50) and PI values of 272 and 1.6, respectively) in the MES test in mice. As well as its anti-MES efficacy, the potencies of compound 8h against seizures induced by pentylenetetrazole and thiosemicarbazide were also established, with the results suggesting that the GABAergic system-mediated mechanisms might be involved in its anticonvulsant activity.
36 citations
TL;DR: New series of perimidine derivatives and fused perimidines were derived from the reaction of ketene aminals 1 and 2 with diazotized anilines or hydrazonoyl chlorides and some products showed promising activity against the human breast cancer cell line MCF‐7 and the liver carcinoma cell line HEPG‐2.
Abstract: New series of perimidine derivatives and fused perimidines were derived from the reaction of ketene aminals 1 and 2 with diazotized anilines or hydrazonoyl chlorides. In addition, 8,10-disubstituted-[1,2,4]triazolo[4,3-a]perimidines (20a-m) were prepared through the reaction of perimidine-2-thione (15) with hydrazonoyl chlorides. The structures of the newly synthesized compounds were established on the basis of spectral data and elemental analyses. Some products were investigated for their antitumor activities against the human breast cancer cell line MCF-7 and the liver carcinoma cell line HEPG-2, and the results of some derivatives showed promising activity.
36 citations
TL;DR: The activity of the reported compounds supports its clinical promise as a component of therapeutic strategies for cancer, for which high concentrations of chemotherapeutic agents are always a major limitation.
Abstract: A new series of benzothiazoles and benzoxazoles was synthesized using 4-benzothiazol-2-yl-phenylamine and 4-benzoxazol-2-yl-phenylamine as starting materials. All the prepared compounds were evaluated for their antitumor activities against human breast cancer cell lines, MCF-7 and MDA-231, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability analysis. Almost all the tested compounds revealed potent antitumor activity, especially the N-methyl piperazinyl substituted derivatives 6f and 6c, which displayed the most potent inhibitory activity with IC50 values ranging from 8 to 17 nM. Docking the synthesized compounds into the epidermal growth factor receptor (EGFR), which is highly expressed in breast cancer, was employed to explore the possible interactions of these compounds with the EGFR. The activity of the reported compounds supports its clinical promise as a component of therapeutic strategies for cancer, for which high concentrations of chemotherapeutic agents are always a major limitation.
35 citations
TL;DR: The formation of neovessels in an in vivo model system like CAM, which is angiogenesis dependent, was observed in the presence of compounds 8a–o, which would help in understanding their putative potential as therapeutic agents for cancer patients.
Abstract: In the current scenario, development of anticancer drugs with specific targets is of prime importance in modern chemical biology. Observing the importance of benzophenone and coumarin nucleus, it would be worthwhile to design and synthesize novel benzophenone derivatives (8a-o) bearing the coumarin nucleus. Further, they were screened for prospective anticancer activities in vitro against the Michigan Cancer Foundation-7 (MCF-7) and Ehrlich's ascites tumor (EAT) cell lines and their biomarkers, followed by in silico studies regarding phosphoinositide 3-kinase (PI3K) and caspase by molecular docking. Benzophenones have been reported as potential drugs targeting tumor angiogenesis; thus, the formation of neovessels in an in vivo model system like CAM, which is angiogenesis dependent, was observed in the presence of compounds 8a-o. The above findings would help in understanding their putative potential as therapeutic agents for cancer patients.
34 citations
TL;DR: The design and synthesis of several new bis‐thiazoles 4a–h serving as bis‐drugs in comparison with mono‐heterocyclic analogs are described and present superior medicinal and pharmacological activities against both gram‐negative and gram‐positive bacteria.
Abstract: The design and synthesis of several new bis-thiazoles 4a-h serving as bis-drugs in comparison with mono-heterocyclic analogs are described. These bis-drugs present superior medicinal and pharmacological activities against both gram-negative (Pseudomonas aeruginosa and Escherichia coli) and gram-positive (Micrococcus luteus and Bacillus subtilis) bacteria, which are in general more sensitive to compounds with higher hydrophobicity. Compounds with higher hydrophobicity (4d and 4h) exhibited some activity against the gram-negative bacteria.
TL;DR: Quantitative structure–activity relationships (QSARs) were developed using CORAL software for four random splits of the data into the training and test sets and reveal good predictive potential of the applied approach.
Abstract: The activity of 72 1,4-dihydropyridines as calcium channel antagonists was examined. The simplified molecular input-line entry system (SMILES) was used as representation of the molecular structure of the calcium channel antagonists. Quantitative structure-activity relationships (QSARs) were developed using CORAL software (http://www.insilico.eu/CORAL) for four random splits of the data into the training and test sets. Using the Monte Carlo method, the CORAL software generated the optimal descriptors for one-variable models. The reproducibility of each model was tested performing three runs of the Monte Carlo optimization. The obtained results reveal good predictive potential of the applied approach: The correlation coefficients (r(2) ) for the test sets of the four random splits are 0.9571, 0.9644, 0.9836, and 0.9444.
TL;DR: 2‐Cyano‐N‐(4,6‐dimethyl‐1H‐pyrazolo[3,4‐b]pyridin‐3‐yl)‐(dimethylamino)acrylamide was synthesized and allowed to react with hydroxylamine, hydrazine, and guanidine to afford regioselectively the isoxazole 13, pyrazole 15, and pyrimidine 17 derivatives, respectively.
Abstract: 2-Cyano-N-(4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl)acetamide (2) was utilized as key intermediate for the synthesis of some new coumarin 3, pyridine 4, pyrrole 5, thiazole 8, pyrido[2',3':3,4]-pyrazolo-[5,1-c]triazine 7, and aminopyrazolo 10 compounds. 2-Cyano-N-(4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-3-(dimethylamino)acrylamide (11) was synthesized and allowed to react with hydroxylamine, hydrazine, and guanidine to afford regioselectively the isoxazole 13, pyrazole 15, and pyrimidine 17 derivatives, respectively. The reaction of 11 with thiourea and/or with ethyl glycinate in basic medium afforded the regioisomeric pyrimidinethione 18 and 3,5-dioxo-1,4-diazepine-6-carbonitrile 23. All the synthesized products were tested and evaluated as antimicrobial agents.
TL;DR: A novel series of mesotetrakis[aryl]‐21H,23H‐porphyrin derivatives 2a-j was synthesized from the condensation of aldehyde derivatives 1a–j with pyrrole in the presence of p‐toluenesulfonic acid and found that these compounds effectively inhibit the free radical‐induced oxidative hemolysis of red blood cells.
Abstract: A novel series of mesotetrakis[aryl]-21H,23H-porphyrin derivatives 2a-j was synthesized from the condensation of aldehyde derivatives 1a-j with pyrrole in the presence of p-toluenesulfonic acid. The synthesized porphyrins were considered as a model to study the free radical-induced damage of biological membranes and the protective effects of these porphyrins. It was found that these compounds effectively inhibit the free radical-induced oxidative hemolysis of red blood cells. Compounds 2c and 2d which bear a sulfur atom, a nitro group, and a chlorine atom exhibited markedly higher antihemolysis activity than the other analogous. Compounds 2a, 2c, 2d, and 2j showed the highest protection activity against DNA damage induced by the bleomycin-iron complex. Compounds 2d, 2f, 2i, and 2j were proved to exhibit antioxidative activity.
TL;DR: A new series of 2‐(4‐(trifluoromethyl)phenyl)‐1H‐benzo[d]imidazole derivatives containing a 1,2,4‐triazole ring were synthesized via microwave technique, providing pure products within a few minutes.
Abstract: A new series of 2-(4-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole derivatives containing a 1,2,4-triazole ring were synthesized via microwave technique. This efficient procedure provides pure products within a few minutes. The newly synthesized compounds were confirmed by (1) H NMR and (13) C NMR spectra and they were screened for their lipase inhibition and antioxidant activities. Compounds 4a, 4b, 5a, and 5b showed very good scavenging activity.
TL;DR: Anticancer screening showed that the cytostatic effects of the 5,6‐dihydroxylated benzo[b]furans were most effective against the melanoma (UACC62) cancer cell line with several compounds exhibiting potent growth inhibitory activities.
Abstract: A commercial laccase, Suberase 1 from Novozymes, was used to catalyse the synthesis of 5,6dihydroxylated benzo[b]furans and catechol derivatives. The yields were, in some cases, similar to or better than that obtained by other enzymatic, chemical or electrochemical syntheses. The synthesised derivatives were screened against renal (TK10), melanoma (UACC62), breast (MCF7) and cervical (HeLa) cancer cell lines. GI50, TGI and LC50 are reported for the first time. Anticancer screening showed that the cytostatic effects of the 5,6-dihydroxylated benzo[b]furans were most effective against the melanoma (UACC62) cancer cell line with several compounds exhibiting potent growth inhibitory activities (GI50 ¼ 0.77‐9.76 mM), of which two compounds had better activity than the anticancer agent etoposide (GI50 ¼ 0.89 mM). One compound exhibited potent activity (GI50 ¼ 9.73 mM) against the renal (TK10) cancer cell line and two exhibited potent activity (GI50 ¼ 8.79 and 9.30 mM) against the breast (MCF7) cancer cell line. These results encourage further studies of the 5,6-dihydroxylated benzo[b]furans for their potential application in anticancer therapy.
TL;DR: Three novel series of 6,8‐dibromo‐4(3H)quinazolinone derivatives were synthesized and tested for their antitumor activity against the human breast carcinoma cell line MCF‐7, with very low IC50 values compared to doxorubicin (positive control).
Abstract: Three novel series of 6,8-dibromo-4(3H)quinazolinone derivatives were synthesized. Some of the novel quinazolinone derivatives were tested for their antitumor activity against the human breast carcinoma cell line MCF-7. Compounds XIIIb, IX, XIVd, XIVb, XIVe, XIIIa, XIVc, XVc, and XIVa exerted powerful cytotoxic effects against the MCF7 cells, with very low IC50 values compared to doxorubicin (positive control). The IC50 values were 1.7, 1.8, 1.83, 5.4, 6.84, 10.8, 13.9, 15.7, and 29.6 µg/mL, respectively.
TL;DR: New pyrazoline derivatives were synthesized via the reaction of 1‐(chloroacetyl)‐3‐(2‐furyl)‐5‐aryl‐2‐pyrazolines with sodium salts of N,N‐disubstituted dithiocarbamic acids using a modification of Ellman's spectrophotometric method.
Abstract: In the present study, new pyrazoline derivatives were synthesized via the reaction of 1-(chloroacetyl)-3-(2-furyl)-5-aryl-2-pyrazolines with sodium salts of N,N-disubstituted dithiocarbamic acids. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using a modification of Ellman's spectrophotometric method. The compounds were also investigated for their cytotoxic properties using the MTT assay. The most potent AChE inhibitor was found as compound 7 followed by compounds 27 and 17, when compared with eserine. Compounds effective on AChE carry the 2-dimethylaminoethyl moiety, which resembles the trimethylammonium group and the ethylene bridge of acetylcholine. Among all compounds, compound 7 bearing 2-dimethylaminoethyl and 3,4-methylenedioxyphenyl moieties was also found to be the most effective inhibitor of BuChE. The MTT assay indicated that the effective concentration of compound 7 was lower than its cytotoxic concentration.
TL;DR: A series of novel cationic fullerene derivatives bearing a substituted‐quinazolin‐4(3H)‐one moiety as a side arm exhibited significant activity, with the most effective compounds having MIC values and zones of inhibition comparable to those of standard drugs.
Abstract: A series of novel cationic fullerene derivatives bearing a substituted-quinazolin-4(3H)-one moiety as a side arm were synthesized using the 1,3-dipolar cycloaddition reaction of C60 with azomethine ylides generated from the corresponding Schiff bases of substituted quinazolinones. The synthesized compounds 5a-f were characterized by elemental analysis, FT-IR, 1H NMR, 13C NMR, and ESI-MS and screened for their antibacterial activity against Mycobacterium tuberculosis (H37RV) and antimicrobial activity against selected Gram-positive (Staphylococcus aureus and S. pyogenes) and Gram-negative (Pseudomonas aeruginosa, Klebsiella pneumonia and Escherichia coli) bacterial and fungal strains (Candida albicans, Aspergillus clavatus, and A. niger), respectively. All the compounds exhibited significant activity, with the most effective compounds having MIC values and zones of inhibition comparable to those of standard drugs.
TL;DR: A new series of 1,3,4‐thiadiazole derivatives (4a–4p) were synthesized and their in vitro anticancer activities were evaluated against three cancer cell lines: PC3 (prostate cancer), MCF7 (breast cancer), and SKNMC (neuroblastoma).
Abstract: In the current research of medicinal chemistry, apoptosis induction is one of the novel strategies for the development and discovery of novel anticancer therapeutics. In the present study, a new series of 1,3,4-thiadiazole derivatives (4a-4p) were synthesized and their in vitro anticancer activities were evaluated against three cancer cell lines: PC3 (prostate cancer), MCF7 (breast cancer), and SKNMC (neuroblastoma). These cell lines were utilized in MTT assays and the obtained results were compared to doxorubicin. Apoptosis induction was also investigated through exploration of the activation of caspases 3, 8, and 9. According to the obtained results, compounds 4b (3-Cl) and 4c (4-Cl) demonstrated the best caspase activation. In fact, compounds 4b and 4c enhanced the activity of caspases 3 and 9 in the MCF7 cell line.
TL;DR: A series of PF‐8380 analogs, a recently developed autotaxin inhibitor, was explored, and analogs 8 and 9, bearing only the benzo[d]oxazol‐2(3H)‐one moiety, are more cytotoxic on the LN229 glioblastoma cell line than PF‐198380 and temozolomide (TMZ).
Abstract: A series of PF-8380 analogs, a recently developed autotaxin inhibitor, was explored. Inhibition of autotaxin by these analogs, as well as by all PF-8380 synthetic intermediates, shows the importance of meta-dichlorobenzyl and benzo[d]oxazol-2(3H)-one fragments. However, analogs 8 and 9, bearing only the benzo[d]oxazol-2(3H)-one moiety, are more cytotoxic on the LN229 glioblastoma cell line than PF-8380 and temozolomide (TMZ).
TL;DR: Within the o‐OMe‐PhP series, except for a small binding reduction for ligands containing the m‐xylyl moiety, there was no substantial change in the compounds' potency at both receptors, while for the THIQ derivatives a clear structure–activity relationship was visible only for the interaction of the compounds with the 5‐HT7 receptor, which strongly favored flexible analogs.
Abstract: A series of new long-chain arylpiperazine (LCAP) derivatives with flexible and partly constrained alkyl linker were synthesized and investigated in vitro as potential serotonin 5-HT(1A) and 5-HT(7) receptor ligands. The compounds were prepared by a two-step procedure using naphthalimide and 2H-1,3-benzoxazine-2,4(3H)-dione as imides, and 1-(2-methoxyphenyl)piperazine (o-OMe-PhP) and 1,2,3,4-tetrahydroisoquinoline (THIQ) as amine pharmacophores. Modifications of the spacer structure included introduction of flexible penta- and hexamethylene chains as well as partly constrained m- and p-xylyl moieties. In general, the new compounds were more active at the 5-HT(1A) than at the 5-HT(7) receptor, and the o-OMe-PhP derivatives displayed higher affinities than their respective THIQ analogs. The spacer modifications had little effect on the observed in vitro activities. Within the o-OMe-PhP series, except for a small binding reduction for ligands containing the m-xylyl moiety, there was no substantial change in the compounds' potency at both receptors, while for the THIQ derivatives a clear structure-activity relationship was visible only for the interaction of the compounds with the 5-HT(7) receptor, which strongly favored flexible analogs.
TL;DR: A novel series of coumarin and 3‐coumaranone derivatives encompassing the phenacyl pyridinium moiety were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinerase (BuE) inhibitory activity using Ellman's method, revealing dual binding site inhibitors of AChE.
Abstract: A novel series of coumarin and 3-coumaranone derivatives encompassing the phenacyl pyridinium moiety were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity using Ellman's method All compounds presented inhibitory activity against both AChE and BuChE in the micromolar range The molecular docking simulations revealed that all compounds were dual binding site inhibitors of AChE A kinetic study was performed and the mechanism of enzyme inhibition was proved to be of mixed type All compounds were tested for their antioxidant activity and no significant activity was observed
TL;DR: Several novel betulin derivates prepared using Mannich reactions as a key step showed significant cytotoxicity; they act by triggering apoptotic cell death as shown by additional acridine orange/propidium iodide assays, Trypan blue tests, DNA laddering experiments, and investigations of the cell cycle.
Abstract: Several novel betulin derivates were prepared using Mannich reactions as a key step. Starting from 3-ethynyl-3-hydroxy-lup-20(29)-ene derivatives, copper-catalyzed Mannich reactions yielded hydroxypropargyl ammonium hydrochlorides or their corresponding methiodides. All compounds were screened in a sulforhodamine B assay for their antitumor activity using a panel of 9 human cancer cell lines. Some of these compounds showed significant cytotoxicity; they act by triggering apoptotic cell death as shown by additional acridine orange/propidium iodide assays, Trypan blue tests, DNA laddering experiments, and investigations of the cell cycle.
TL;DR: The in vitro photodynamic activity demonstrated that, as the degree of bromination increased, the phototoxicity remained unchanged or decreased, and a promising strategy to reverse the biological activity decrease observed might be the design of third‐generation photosensitizers.
Abstract: Triarylmethane and thiazine dyes have attracted attention as anticancer and antimicrobial agents, due to their structural features and selective localizations. Although these dyes have been initially explored in the context of photodynamic therapy, some of these such as New Fuchsin and Azure B have still not been extensively investigated. For this reason, we evaluated the chemical stability, aggregation effect, and lipophilicity, as well as the photodynamic activity against LM-2 murine mammary carcinoma cells of five new brominated dyes of triarylmethane and thiazine. These cationic compounds were obtained at high purities and unequivocally characterized by conventional techniques. The introduction of bromine atoms into the chromophoric system of New Fuchsin and Azure B dyes gave rise to a moderate bathochromic shift and increased the lipophilicity, thereby improving their photophysical and photochemical properties for biomedical applications. Moreover, the in vitro photodynamic activity demonstrated that, as the degree of bromination increased, the phototoxicity remained unchanged or decreased. The lower efficiency to inactivate cultured tumor cells may be attributed to the formation of the colorless carbinol pseudobase and aggregation effects for triarylmethane and thiazine dyes, respectively. A promising strategy to reverse the biological activity decrease observed might be the design of third-generation photosensitizers.
TL;DR: The structure of (Z)‐3‐benzyl‐4‐(4‐bromophenyl)‐2‐[(E)‐(1‐phenylethylidene)hydrazono]‐2,3‐dihydrothiazole 6e was unambiguously confirmed by single‐crystal X‐ray crystallography.
Abstract: (E)-4-Aryl-2-[2-(1-substituted ethylidene)hydrazinyl]thiazoles and (Z)-3-substituted-4-aryl-2-[(E)-(1-phenylethylidene)hydrazono]-2,3-dihydrothiazoles were synthesized by the reaction of (substituted ethylidene)hydrazinecarbothioamides with ω-bromoacetophenones. The characterization of this new class of compounds was performed using different spectroscopic tools. The structure of (Z)-3-benzyl-4-(4-bromophenyl)-2-[(E)-(1-phenylethylidene)hydrazono]-2,3-dihydrothiazole 6e was unambiguously confirmed by single-crystal X-ray crystallography. Compounds 5a-e, 5i, 6e, 6g, and 6i were screened for their in vitro antibacterial activity against different strains of microorganisms; most of the tested compounds exhibited promising antibacterial activity against some organisms compared to ciprofloxacin and sulbactam penicillin. Compounds 5e, 5i, 6e, 6g, and 6i exhibited several-fold significant antibacterial activity against the Gram-positive bacteria Staphylococcus aureus, better than ciprofloxacin, with minimum inhibitory concentration values ranging from 0.05 to 0.4 µg/mL. The rest of the tested compounds gave significant antibacterial activities against different Gram-negative bacterial strains.
TL;DR: The biological activity studies revealed that all the compounds screened showed good or moderate antimicrobial, antiurease, and/or antilipase activity.
Abstract: 4-Aryl-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-(thi)oles 5-7, obtained starting from nicotinic acid hydrazide were converted to the corresponding Mannich bases 12-24 by the reaction with several heterocyclic amines in the presence of formaldehyde The synthesis of S-alkylated compounds 8-11 was performed from the reaction of the corresponding triazol-5-thioles with various alkyl halides The condensation of carbo(thio)amides 2-4 with 4-chlorophenacyl bromide afforded the corresponding 1,3-thia(oxa)zol-2(3H)-ylidene]pyridine-3-carbohydrazides 25-27 1,3-Thia(oxa)zolidine derivatives 28-30 were obtained from the cyclization reaction between compounds 2-4 and ethyl bromoacetate All newly synthesized compounds were screened for their antimicrobial, antiurease, and antilipase activities The biological activity studies revealed that all the compounds screened showed good or moderate antimicrobial, antiurease, and/or antilipase activity
TL;DR: A new class of mono‐ and bis‐heterocycles, 2‐arylsulfonylaminosulfonylmethyl‐5‐styrylmethyloxadiazoles, were synthesized and tested for their antioxidant activity.
Abstract: A new class of mono- and bis-heterocycles, 2-arylsulfonylaminosulfonylmethyl-5-styrylsulfonylmethyloxadiazoles, pyrazolyl oxadiazoles, and isoxazolyl oxadiazoles, were synthesized and tested for their antioxidant activity. The styrylsulfonylmethyloxadiazole 5b showed good antioxidant activity when compared with the standard ascorbic acid.
TL;DR: Most of the synthesized compounds exhibited considerable selectivity against the MCF‐7 and C6 cell lines and anticancer activities were investigated.
Abstract: The synthesis of some new 1-(2-aryl-2-oxoethyl)-2-[(morpholine-4-yl)thioxomethyl]benzimidazole derivatives and investigation of their anticancer activities were the aims of this work. 2-(Chloromethyl)benzimidazole compound was reacted with sulfur and morpholine via Willgerodt–Kindler reaction to give 2-[(morpholine-4-yl)thioxomethyl]benzimidazole. Then, the obtained compound was reacted with appropriate a-bromoacetophenone derivatives in the presence of potassium carbonate to give the final products. Structure elucidation of the final compounds was achieved by FT-IR, 1 H NMR spectroscopy and MS spectrometry. The anticancer activities of the final compounds were evaluated by MTT assay, BrdU method, and flow cytometric analysis on C6, MCF-7, and A549 tumor cells. Most of the synthesized compounds exhibited considerable selectivity against the MCF-7 and C6 cell lines.
TL;DR: Novel polyhydroxylated (E)‐stilbenes were synthesized by Mizoroki–Heck reactions and tested for their ability to inhibit the enzymes acetyl‐ and butyrylcholinesterase.
Abstract: Novel polyhydroxylated (E)-stilbenes were synthesized by Mizoroki-Heck reactions and tested for their ability to inhibit the enzymes acetyl- and butyrylcholinesterase. Several of them are good inhibitors of butyrylcholinesterase; one of them carrying an extra fluorine substituent is a 94-fold stronger inhibitor of butyrylcholinesterase than of acetylcholinesterase.