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In the present study novel 1,2,4-oxadiazolo sulfonamides 3a-3o are synthesized by an efficient method based on the reaction of 1,2,4-oxadiazole amines with aryl sulfonyl chlorides. Structures of the synthesized compounds are confirmed by IR, NMR and Mass spectra. Molecular interactions of the obtained compounds are studied by Discovery Studio v3.5, molecular docking with COX-2 enzyme. The compounds with high LibDock score are screened for their in vivo analgesic and anti inflammatory activities. The compound 3l demonstrates the highest activity. [ABSTRACT FROM AUTHOR]

The corticotropin-releasing factor (CRF) system is a key mediator of the stress response and addictive behavior. The CRF system includes four peptides: The CRF system includes four peptides: CRF, urocortins I-III, CRF binding protein (CRF-BP) that binds CRF with high affinity, and two class B G-protein coupled receptors CRF1R and CRF2R. CRF-BP is a secreted protein without significant sequence homology to CRF receptors or to any other known class of protein. Recently, it has been described a potentiation role of CRF-BP over CRF signaling through CRF2R in addictive-related neuronal plasticity and behavior. In addition, it has been described that CRF-BP is capable to physically interact specifically with the α isoform of CRF2R and acts like an escort protein increasing the amount of the receptor in the plasma membrane. At present, there are no available structures for CRF-BP or for full-length CRFR. Knowing and studying the structure of these proteins could be beneficial in order to characterize the CRF-BP/CRF2αR interaction. In this work, we report the modeling of CRF-BP and of full-length CRF2αR and CRF2βR based on the recently solved crystal structures of the transmembrane domains of the human glucagon receptor and human CRF1R, in addition with the resolved N-terminal extracellular domain of CRFRs. These models were further studied using molecular dynamics simulations and protein-protein docking. The results predicted a higher possibility of interaction of CRF-BP with CRF2αR than CRF2βR and yielded the possible residues conforming the interacting interface. Thus, the present study provides a framework for further investigation of the CRF-BP/CRF2αR interaction. [ABSTRACT FROM AUTHOR]

This study reports three novel sulfonamide derivatives 4-Chloro-N-[(4-methylphenyl) sulphonyl]-N-propyl benzamide (1A), N-(2-hydroxyphenyl)-4-methyl benzene sulfonamide (1B) and 4-methyl-N-(2-nitrophenyl) benzene sulfonamide (1C). The compounds were synthesised from starting material 4-methylbenzenesulfonyl chloride and their structure was studied through 1H-NMR and 13C-NMR spectra. Computational docking was performed to estimate their binding energy against bacterial p-amino benzoic acid (PABA) receptor, the dihydropteroate synthase (DHPS). The derivatives were tested in vitro for their antimicrobial activity against Gram+ and Gram- bacteria including E. coli, B. subtilis, B. licheniformis and B. linen. 1A was found active only against B. linen; 1B was effective against E. coli, B. subtilis and B. linen whereas 1C showed activity against E. coli, B. licheniformis and B. linen. 1C showed maximum activity with minimum inhibitory concentration (MIC) of 50, 100 and 150 µg/mL against E. coli, B. licheniformis and B. linen respectively. 1C exhibited maximum affinity to DHPS with binding free energy of -8.1 kcal/mol. It enriched in the top 0.5% of a library of 7663 compounds, ranked in order of their binding affinity against DHPS. 1C was followed by 1B which showed a moderate to low level MIC of 100, 250 and 150 µg/mL against E. coli, B. subtilis and B. linen respectively, whereas 1A showed a moderate level MIC of 100 µg/mL but only against B. linen. These derivatives may thus serve as potential antibacterial alternatives against resistant pathogens. [ABSTRACT FROM AUTHOR]

Candidiasis represent a serious threat for patients with altered immune responses. Therefore, we have undertaken the synthesis of compounds comprising a pyridine-3-sulfonamide scaffold and known antifungally active 1,2,4-triazole substituents. Thus a series of novel 4-substituted N-(5-amino-1H-1,2,4-triazol-3-yl)pyridine-3-sulfonamides have been synthesized by multistep reactions starting from 4-chloropyridine-3-sulfonamide via N'-cyano-N-[(4- substitutedpyridin-3-yl)sulfonyl]carbamimidothioates which were further converted with hydrazine hydrate to the corresponding 1,2,4-triazole derivatives 26-36. The final compounds were evaluated for antifungal activity against strains of the genera Candida, Geotrichum, Rhodotorula, and Saccharomycess isolated from patients with mycosis. Many of them show greater efficacy than fluconazole, mostly towards Candida albicans and Rhodotorula mucilaginosa species, with MIC values ≤ 25 μg/mL. A docking study of the most active compounds 26, 34 and 35 was performed showing the potential mode of binding to Candida albicans lanosterol 14α-demethylase. Also in vitro cytotoxicity of selected compounds have been evaluated on the NCI-60 cell line panel. [ABSTRACT FROM AUTHOR]

Sixteen Schiff bases of quinazolin-4-one-linked 1,3,4-oxadiazoles were synthesized by reaction with different aromatic aldehydes. Purity of newly synthesized derivatives was confirmed through thin-layer chromatography, combustion analysis, and melting point. The structure of the derivatives was confirmed by determining infrared spectroscopy, nuclear magnetic resonance, and mass spectroscopy. All the synthesized derivatives were evaluated for their analgesic and anti-inflammatory activities in mice and rats, respectively. In animal studies, the derivative ( E)-3-(5-(4-(4-methoxybenzylideneamino)phenyl)-1,3,4-oxadiazol-2-yl)-2-phenylquinazolin-4(3 H)-one showed more potent analgesic activity and the derivative ( Z)-3-(5-(2-(2-hydroxybenzylideneamino)phenyl)-1,3,4-oxadiazol-2-yl)-2-phenylquinazolin-4(3 H)-one showed more potent anti-inflammatory activity as compared with other derivatives. The results of the present study indicate that reactions of 3-(5-(4-aminophenyl)-1,3,4-oxadiazol-2-yl)-2-phenylquinazolin-4(3 H)-one and 3-(5-(2-aminophenyl)-1,3,4-oxadiazol-2-yl)-2-phenylquinazolin-4(3 H)-one with different aromatic aldehydes produce Schiff bases of quinazolin-4-one-linked 1,3,4-oxadiazoles with potent analgesic and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

The development of new catalyst-free green and efficient protocol to access 5′-thioxospiro[indoline-3,3′-[1,2,4]triazolidin]-2-ones/spiro[indoline-3,3′-[1,2,4]triazolidine]-2,5′-diones, potential privileged scaffolds for drug discovery, is disclosed. Key feature of this methodology is the dual use of glycerol—a recyclable, bioorganic compound, as a solvent cum promoter. Other highlights include use of inexpensive reagents, mild reaction conditions, operational simplicity, short reaction time, no need for chromatographic purification, and high yields. [ABSTRACT FROM PUBLISHER]

Connexin37 (Cx37) is a gap junction protein involved in cell-to-cell communication in the vasculature and other tissues. Cx37 suppresses proliferation of vascular cells involved in tissue development and repair in vivo, as well as tumor cells. Global deletion of Cx37 in mice leads to enhanced vasculogenesis in development, as well as collateralgenesis and angiogenesis in response to injury, which together support improved tissue remodeling and recovery following ischemic injury. Here we report the H, N, and C resonance assignments for an important regulatory domain of Cx37, the carboxyl terminus (CT; C233-V333). The predicted secondary structure of the Cx37CT domain based on the chemical shifts is that of an intrinsically disordered protein. In the H-N HSQC, N-terminal residues S254-Y259 displayed a second weaker peak and residues E261-Y266 had significant line broadening. These residues are flanked by prolines (P250, P258, P260, and P268), suggesting proline cis-trans isomerization. Overall, these assignments will be useful for identifying the binding sites for intra- and inter-molecular interactions that affect Cx37 channel activity. [ABSTRACT FROM AUTHOR]

Several phthalazine derivatives were synthesized by the one-pot three-component condensation in good to high yields in the presence of diatomite- $$\hbox {SO}_{3}\hbox {H}$$ as a solid acid catalyst. Then, a series (n = 14) of phthalazine sulfonamides were synthesized by the reaction phthalazine sulfonyl chloride and various amines under solvent-free conditions. The prepared compounds were screened for antibacterial activity against Escherichia coli (E. coli ATCC 25922) and Staphylococcus aureus ( S. aureus ATCC 5213) as gram negative and positive respectively. Also, in silico physicochemical parameters of synthesized compounds were studied to predict absorption and permeability using Molinspiration online property calculation server. Graphical abstract : SYNOPSIS A series of phthalazine sulfonamides were synthesized by the reaction phthalazine sulfonyl chloride and various amines under solvent-free conditions by the one-pot three-component condensation in good to high yields in the presence of diatomite- $$\hbox {SO}_{3}\hbox {H}$$ as a solid acid catalyst. [ABSTRACT FROM AUTHOR]

Several new heterocyclic compounds such as 7-substituted pyrazolo[1,5- a]pyrimidine ( 5a-e) derivatives have been synthesized by the reactions of the versatile unreported sodium 3-(4-methyl-2-(4-methylphenylsulfonamido)thiazol-5-yl)-3-oxoprop-1-en-1-olate (2) with amino heterocyclic ( 3a-e) derivatives. Reaction of (2) with hydrazonyl halide ( 7a-d) and hydroximoyl chloride ( 11a,b) derivatives followed by reaction with hydrazine hydrate afforded pyrazolo[3,4- d]pyridazine and isoxazolo[3,4- d]pyridazine derivatives, respectively incorporating a thiazole moiety have been described. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis. [ABSTRACT FROM AUTHOR]

Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1H-benzimidazol-2-yl)phenyl)-4-substituted-4H-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against Candida species. The synthesized compounds were characterized and elucidated by FT-IR, 1H-NMR, 13C-NMR and HR-MS spectroscopies. The synthesized compounds were screened in vitro anticandidal activity against Candida species by broth microdiluation methods. In vitro cytotoxic effects of the final compounds were determined by MTT assay. Microbiological studies revealed that compounds 5m, 5o, 5r, 5ţ 5y, 5ab, and 5ad possess a good antifungal profile. Compounds 5w was the most active derivative and showed comparable antifungal activity to those of reference drugs ketoconazole and fluconazole. Cytotoxicity evaluation of compounds 5m, 5o, 5r, 5w, 5y, 5ab and 5ad showed that compounds 5w and 5ad were the least cytotoxic agents. Effects of these two compounds against ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of ergosterol level in C. albicans. Compounds 5w and 5d inhibited ergosterol biosynthesis concentration dependently. A fluorescence microscopy study was performed to visualize effect of compound 5w against C. albicans at cellular level. It was determined that compound 5w has a membrane damaging effecţ which may be related with inhibition of biosynthesis of ergosterol. [ABSTRACT FROM AUTHOR]

Polypyrrole chitosan core shell nanoparticles were synthesized by in situ oxidation polymerization of pyrrole using FeCl3 in chitosan aqueous solution. 5-Phenyl-4H-1,2,4-triazole-3-thiol (I) was prepared and loaded into polypyrrole chitosan core shell nanoparticles at two different temperatures (25°C and 80°C). These core shell nanoparticle systems are insoluble in acidic medium and have good adsorption capacity. The release of loaded triazole was studied in different pH media (2, 7.4). The mechanism of triazole release was determined by applying zero-order release, first-order release, Higuchi model, Hixson–Crowell, and Korsmeyer–Peppas kinetics equations. The antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis were evaluated. The potential cytotoxicity against Ehrlich ascites carcinoma cells and liver (HEPG2) cell line in vitro was tested. [ABSTRACT FROM AUTHOR]

A synthesis of novel three-, four-, and sixfold branched 4-phenylthiazolylhydrazones, 4-pyrazolylthiazolyl hydrazones, and thiadiazoles which are linked to a benzene core via phenoxymethyl spacers was reported. The synthetic methodology includes initially formation of poly(aldehyde thiosemicarbazones) 9, 14, and 15 by acid catalyzed condensation of thiosemicarbazide ( 8) with the appropriate poly(aldehydes) 3, 5, and 7, respectively. Subsequent reaction of 9, 14, and 15 with each of 2-bromo-1-phenylethanone ( 10a) and 2-bromo-1-( 4-chlorophenyl)ethanone ( 10b) in refluxing ethanol in the presence of few drops of TEA afforded 11, 16, and 18, respectively, in good yields. On the other hand, the synthesis of the novel poly(4,5-dihydro-1,3,4-thiadiazolyl) derivatives 20, 21a, 21b, and 22 was performed by of 9b, 14a, 14b, and 15a, respectively, in refluxing . [ABSTRACT FROM AUTHOR]

N-{( E)-(dimethylamino)methylidenearbamothioyl}-4-toluenesulfonamide ( 2) was obtained by reaction of N-carbamothioyl-4-toluenesulfonamide ( 1) with dimethylformamide dimethylacetal or alternatively by the reaction of 1-(dimethylamino)methylidenethiourea with tosyl chloride. Compound 2 was reacted with substituted anilines to yield anilinomethylidine derivatives 3a, 3b, 3c, 3d, 3e, 3f, 3g. Treatment of 3a, 3b, 3c, 3d, 3e, 3f, 3g with phenacyl bromide gave triazepines 4a, 4b, 4c, 4d, 4e, 4f, 4g and imidazoles 5a, 5b, 5c, 5d, 5e, 5f, 5g. of compound 3e afforded ester derivative 6, which was subjected to react with hydrazine to yield hydrazide derivative 7. Oxadiazole 8 was obtained by reaction of 7 with CS2/KOH. Compound 3e was treated with o-aminophenol or o-aminothiophenol to give benzazoles 9a, 9b. N-(Diaminomethylidene)-4-toluenesulfonamide ( 10) reacted with enaminones to yield pyrimidines 11, 12, 13, respectively. The structures of the compounds were elucidated by elemental and spectral analyses. Some selected compounds were screened for their in vitro antifungal activity. In general, the newly synthesized compounds showed good antifungal activity. [ABSTRACT FROM AUTHOR]

A synthesis of novel bis(triazolothiadiazines) 11, 12, 13, 14, bis(quinoxalines) 16 and 17, bis(thiadiazoles) 24 and 25, and bis(oxadiazole) 31, which are linked to the thieno[2,3- b]thiophene core via phenoxymethyl group, was reported. Thus, reaction of the bis( α-bromoketones) 6 and 7 with the corresponding 4-amino-3-mercapto-1,2,4-triazole derivatives 8, 9, 10 in ethanol-DMF mixture in the presence of a few drops of triethylamine as a catalyst under reflux afforded the novel bis(5,6-dihydro- s-triazolo[3,4- b]thiadiazines) 11, 12, 13, 14 in 60-72% yields. The bis(quinoxalines) 16 and 17 were also synthesized as a sole product in high yields by the reaction of 6 and 7 with o-phenylenediamine 15 in refluxing acetonitrile in the presence of piperidine as a catalyst. of the bis(aldehyde thiosemicarbazones) 20 and 21 with afforded the corresponding bis(4,5-dihydro-1,3,4-thiadiazolyl) derivatives 24 and 25 in good yield. Bis(5-phenyl-2,3-dihydro-1,3,4-oxadiazole) derivative 31 could be obtained in 67% yield by of the appropriate bis( N-phenylhydrazone) 29 in refluxing for 3 h. [ABSTRACT FROM AUTHOR]

In the recent times, many people around the world are suffering drug resistant in most of the antibiotics used in different circumferences. In order to overcome the antibiotic resistance problem, there is need to use of existing antibiotics consciously and prepare novel compounds which exhibit high therapeutic profile against different pathogens with least resistance. In this review we discussed the thiadiazole derivatives and their different biological activities such as anti-inflammatory, anti-helicobacter pylori, anti-microbial, anti-cancer, antiviral, anti-depressant, analgesic, herbicidal and adenosine A3 receptor inhibitor, besides that this review also provides a detailed information about structural activity relationship (SAR) of such a compounds prepared by different medicinal chemist to date. In general, SAR is the smartest tool among the medicinal chemist to create a better therapeutic efficacy and high safety bioactive molecule in a short span of time. Besides that, we pointed out here different challenges of thiadiazole derivatives and its feature perspectives. [ABSTRACT FROM AUTHOR]

Novel enantiopure 1,2,4-trizole-3-thiones containing a benzensulfonamide moiety were synthesized via multistep reaction sequence starting with D-phenylalanine methyl ester and L-phenylalanine ethyl ester as a source of chirality. The chemical structures of all compounds were characterized by elemental analysis, UV, IR, 1H NMR, 13C NMR, 2D NMR (HETCOR), and mass spectral data. All compounds were tested in vitro antiviral activity against a broad variety of DNA and RNA viruses and in vitro cytostatic activity against murine leukemia (L1210), human T-lymphocyte (CEM) and human cervix carcinoma (HeLa) cell lines. Although enantiopure 1,2,4-triazole-3-thione analogs in ( R) configuration emerged as promising anti-influenza A H1N1 subtype in Madin Darby canine kidney cell cultures (MDCK), their enantiomers exhibited no activity. Especially compounds 18a, 21a, 22a, 23a, and 24a (EC50: 6.5, 6.1, 2.4, 1.6, 1.7 μM, respectively) had excellent activity against influenza A H1N1 subtype compared to the reference drug ribavirin (EC50: 8.0 μM). Several compounds have been found to inhibit proliferation of L1210, CEM and HeLa cell cultures with IC50 in the 12-53 μM range. Compound 5a and 27a in ( R) configuration were the most active compounds (IC50: 12-22 μM for 5a and IC50: 19-23 μM for 27a). Chirality 28:495-513, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT Glutathione (GSH) structure-guided tripeptide analogues were designed and synthesized by solid phase technology, purified (≥95%) by RP and/or GF column chromatography, to identify those that, compared with GSH, exhibited similar or higher binding and catalytic efficiency toward the MDR-involved human GSTP1-1 isoenzyme, and could discriminate between the allozymic expression products of the polymorphic human GSTP1 gene locus, designated as hGSTP1*A (Ile104/Ala113), hGSTP1*B (Val104/Ala113), and hGSTP1*C (Val104/Val113). The analogues bear single amino acid alterations as well as alterations in more than one position. Some analogues showed remarkable allozyme selectivity, binding catalytically to A ( I, II, IV, XII), to C ( V and XVI), to A and C ( III, VII, XIV) or to all three allozymes ( XV). A heterocyclic substituent at positions 1 or 2 of GSH favors inhibition of A, whereas a small hydrophobic/hydrophilic amide substituent at position 2 (Cys) favors inhibition of B and C. Heterocyclic substituents at position 1, only, produce catalytic analogues for A, whereas less bulky and more flexible hydrophobic/hydrophilic substituents, at positions 1 or 3, lead to effective substrates with C. When such substituents were introduced simultaneously at positions 1 and 3, the analogues produced have no catalytic potential but showed appreciable inhibitory effects, instead, with all allozymes. It is anticipated that when GSH analogues with selective inhibitory or catalytic binding, were conjugated to allozyme-selective inhibitors of hGSTP1-1, the derived leads would be useful for the designing of novel chimeric inhibitors against the MDR-involved hGSTP1-1 allozymes. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 330-344, 2016. [ABSTRACT FROM AUTHOR]

A new series of sulfonylcycloureas derivatives have been synthesized and evaluated in vitro for their antitumor activity against four cancer cell lines (A431, Jurkat, U266, and K562). These compounds were prepared by the condensation of several sulfonamides ( 2a-m) with ethyl bis(2-chloroethyl)carbamate ( 1a). The relative cytotoxicity of these new derivatives in comparison to chlorambucil is reported. [ABSTRACT FROM AUTHOR]

Microbial resistance to the available drugs poses a serious threat in modern medicine. We report the design, synthesis andin vitroantimicrobial evaluation of new functionalized 2,3-dihydrothiazoles and 4-thiazolidinones tagged with sulfisoxazole moiety. Compound8dwas most active againstBacillis subtilis(MIC, 0.007 µg/mL). Moreover, compounds7c–dand8cdisplayed significant activities againstB. subtilisandStreptococcus pneumoniae(MIC, 0.03–0.06 µg/mL and 0.06–0.12 µg/mL versus ampicillin 0.24 µg/mL and 0.12 µg/mL; respectively). Compounds7aand7c–dwere highly potent againstEscherichia coli(MIC, 0.49–0.98 µg/mL versus gentamycin 1.95 µg/mL). On the other hand, compounds7eand9cwere fourfolds more active than amphotericin B againstSyncephalastrum racemosum. Molecular docking studies showed that the synthesized compounds could act as inhibitors for the dihydropteroate synthase enzyme (DHPS). This study is a platform for the future design of more potent antimicrobial agents. [ABSTRACT FROM AUTHOR]

ABSTRACT Pmel17 is the major component of functional amyloid fibrils that have an important role during pigment deposition. Pmel17 polymerization is promoted within the mildly acidic conditions of melanosomes, organelles located in pigment-specific cells. A repeat domain (RPT domain) of Pmel17, rich in glutamic acid residues has been extensively associated with the formation of the fibrous matrix. Here, we examine the RPT domain of human Pmel17 in order to provide information on this mechanism. Specifically, we have identified an aggregation-prone peptide segment (405VSIVVLSGT413), close to the C-terminal part of the RPT domain. Experimental results utilizing electron microscopy, X-ray fiber diffraction, Congo red staining and ATR FT-IR spectroscopy indicate that this peptide segment self-assembles forming fibrils with evident amyloidogenic properties. Conclusively, our results demonstrate that the 405VSIVVLSGT413 peptide segment possibly has an essential role in RPT domain fibrillogenesis. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 133-139, 2016. [ABSTRACT FROM AUTHOR]

ABSTRACT CD2 and CD58 are two important costimulatory molecules involved in generating the signal II required for normal immune signaling. However, this interaction can be targeted to be of benefit in cases of abnormal immune signaling seen in autoimmune diseases. Our objective in this study was to design a peptidomimetic (compound 7) based on a β-strand structure of the adhesion domain of CD2 protein to inhibit CD2-CD58 protein-protein interaction and its effect on immunomodulation in the collagen-induced arthritis (CIA) model. The ability of compound 7 to bind to CD58 protein was assessed using flow cytometry. The effect of compound 7 on modulating the immune response was evaluated in an autoimmune disease using CIA in mice. The stability of compound 7 was evaluated in mouse serum using mass spectrometry. Antibody (Ab) binding inhibition studies suggested that compound 7 binds to CD58 protein. Compound 7 was successful in modulating immune responses when administered in the CIA mouse model along with reducing anti-collagen Ab levels and decreasing the level of interferon gamma (IFN-γ) relative to control treatments. Compound 7 was found to be nonimmunogenic and stable in mouse serum up to 48 h. Results suggest that compound 7 can serve as a lead compound for immunomodulation, and could be a therapeutic agent for the autoimmune disease rheumatoid arthritis (RA). © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 733-742, 2015. [ABSTRACT FROM AUTHOR]

A novel series of alloxan-derived 1,4-disubstituted 1,2,3-triazoles was synthesized in excellent yields under catalytic conditions using a click reaction strategy through 1,3-dipolar cycloaddition. Their structures have been ascertained on the basis of spectroanalytical and elemental analysis data. Synthesis of hybrid compounds with varying substitutions in the triazole ring was achieved by reaction between alloxan-derived terminal alkyne and a pertinent azide derivative in the presence of clay-Cu(II) as the catalyst in methanolic medium. Also, comparative evaluation of various catalytic systems [viz., CuI, CuSO4, CuI-zeolite, K10Ti, and clay-Cu(II)] was investigated. Of these catalytic systems, clay-Cu(II) was observed to be the best. The catalyst was recyclable for several runs without showing significant loss in its activity. The good selectivity, cost-efficiency, short reaction time, milder reaction conditions, and simple workup procedure are the added salient features of this synthetic protocol. [ABSTRACT FROM AUTHOR]

The selectivity of certain benzophenones and their carbonyl N-analogues was investigated towards the human GSTP1-1 allozymes A, B and C involved in MDR. The allozymes were purified from extracts derived from E. coli harbouring the plasmids pEXP5- CT/ TOPO- TA- hGSTP1*A, pOXO4- hGSTP1*B or pOXO4- hGSTP1*C. Compound screening with each allozyme activity indicated three compounds with appreciable inhibitory potencies, 12 and 13 with P1-1A 62% and 67%, 11 and 12 with P1-1C 51% and 70%, whereas that of 15 fell behind with P1-1B (41%). These findings were confirmed by IC50 values (74-125 μ m). Enzyme inhibition kinetics, aided by molecular modelling and docking, revealed that there is competition with the substrate CDNB for the same binding site on the allozyme ( Ki(13/A) = 63.6 ± 3.0 μ m, Ki(15/B) = 198.6 ± 14.3 μ m, and Ki(11/C) = 16.5 ± 2.7 μ m). These data were brought into context by an in silico structural comparative analysis of the targeted proteins. Although the screened compounds showed moderate inhibitory potency against hGSTP1-1, remarkably, some of them demonstrated absolute isoenzyme and/or allozyme selectivity. [ABSTRACT FROM AUTHOR]

The enzymatic stability, antitumor activity, and gonadotropin stimulatory effects of glycosylated luteinizing hormone-releasing hormone (LHRH) analogs were investigated in this study. Conjugation of carbohydrate units, including lactose (Lac), glucose (GS), and galactose (Gal) to LHRH peptide protected the peptide from proteolytic degradation and increased the peptides' half-lives in human plasma, rat kidney membrane enzymes, and liver homogenate markedly. Among all seven modified analogs, compound 1 (Lac-[Q][w]LHRH) and compound 6 (GS-[w]LHRH) were stable in human plasma during 4 h of experiment. The half-lives of compounds 1 and 6 improved significantly in kidney membrane enzymes (from 3 min for LHRH to 68 and 103 min, respectively). The major cleavage sites for most of the glycosylated compounds were found to be at Trp-Ser and Ser-Tyr in compounds 1-5. Compound 6 was hydrolyzed at Ser-Tyr and the sugar conjugation site. The antiproliferative activity of the glycopeptides was evaluated on LHRH receptor-positive prostate cancer cells. The glycosylated LHRH derivatives had a significant growth inhibitory effect on the LNCaP cells after a 48-h treatment. It was demonstrated that compound 1 significantly increased the release of luteinizing hormone (LH) at 5 and 10 nM concentrations and compound 5 (GS-[Q]LHRH) stimulated the release of follicle-stimulating hormone (FSH) at 5 nM concentration in dispersed rat pituitary cells ( p < 0.05). In our studies, compound 1-bearing lactose and d-Trp was the most stable and active and is a promising candidate for future preclinical investigations in terms of in vitro biological activity and metabolic stability. [ABSTRACT FROM AUTHOR]

Conformational properties of the angiotensin II precursor, angiotensin I (AngI) and analogues containing the paramagnetic amino acid TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) at positions 0, 1, 3, 5, 8, 9, and 10, were examined by EPR, CD, and fluorescence. The conformational data were correlated to their activity in muscle contraction experiments and to their properties as substrates of the angiotensin I-converting enzyme (ACE). Biological activity studies indicated that TOAC0-AngI and TOAC1-AngI maintained partial potency in guinea pig ileum and rat uterus. Kinetic parameters revealed that only derivatives labeled closer to the N-terminus (positions 0, 1, 3, and 5) were hydrolyzed by ACE, indicating that peptides bearing the TOAC moiety far from the ACE cleavage site (Phe8-His9 peptide bond) were susceptible to hydrolysis, albeit less effectively than the parent compound. CD spectra indicated that AngI exhibited a flexible structure resulting from equilibrium between different conformers. While the conformation of N-terminally-labeled derivatives was similar to that of the native peptide, a greater propensity to acquire folded structures was observed for internally-labeled, as well as C-terminally labeled, analogues. These structures were stabilized in secondary structure-inducing agent, TFE. Different analogues gave rise to different β-turns. EPR spectra in aqueous solution also distinguished between N-terminally, internally-, and C-terminally labeled peptides, yielding narrower lines, indicative of greater mobility for the former. Interestingly, the spectra of peptides labeled at, or close, to the C-terminus, showed that the motion in this part of the peptides was intermediate between that of N-terminally and internally-labeled peptides, in agreement with the suggestion of turn formation provided by the CD spectra. Quenching of the Tyr4 fluorescence by the differently positioned TOAC residues corroborated the data obtained by the other spectroscopic techniques. Lastly, we demonstrated the feasibility of monitoring the progress of ACE-catalyzed hydrolysis of TOAC-labeled peptides by following time-dependent changes in their EPR spectra. [ABSTRACT FROM AUTHOR]

The ( Z)/( E) equilibria in water solutions of five ACE inhibitors (captopril, enalapril, lisinopril, perindopril, and ramipril) in presence and in absence of surfactants (anionic sodium dodecyl sulfate, cationic cetyltrimethyl ammonium bromide, and non-ionic 4-octylphenol polyethoxylate) were analyzed by reversed-phase high-performance liquid chromatography. The results showed that the ( Z)/( E) equilibrium of lisinopril and captopril was the least sensitive to the effect of the examined surfactants. 4-Octylphenol polyethoxylate expressed the weakest effect on isomerization of the ACE inhibitors, while the ( Z)/( E) equilibria of enalapril, ramipril, and perindopril were the most sensitive to the presence of sodium dodecyl sulfate and cetyltrimethyl ammonium bromide. In addition, the response of two structurally very close compounds, such as enalapril and ramipril to the presence of sodium dodecyl sulfate and cetyltrimethyl ammonium bromide was opposite, and these two ACE inhibitors had different chromatographic behavior. To provide a better insight into the reasons for the differences in order of elution of ( Z)- and ( E)-diastereomers and the possible molecular mechanism underlying their retention, ( Z)- and ( E)-diastereomers of enalapril and ramipril were subjected to a theoretical study optimized at the B3LYP/6−31G (d,p) level of density functional theory. The Connolly solvent-excluded volume was taken as the most significant parameter that can be connected to differences in chromatographic behavior of the ( Z)- and ( E)-diastereomers of enalapril and ramipril. Graphical abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The present paper elicits an unprecedented synthesis of a novel series of 1,2,3-triazole compounds using geraniol as the precursor via 1,3-dipolar cycloaddition using click chemistry strategy. All the synthesized compounds were screened to evaluate their microbicidal and antioxidant potentials. The antibacterial activity of all the new compounds was assessed by the micro-broth dilution technique against a panel of Gram-positive Staphylococcus aureus (MTCC 3160), Bacillus cereus (MTCC 430), and Gram-negative Escherichia coli (MTCC 1610) and Pseudomonas aeruginosa (MTCC 2295). Furthermore, evaluation of their antioxidative behavior manifested the remarkable free radical scavenging activity using DPPH assay. Also, the docking study of the compounds was performed on complex structure of E.coli FabH (1HNJ. pdb) using VLife MDS 3.5 software. Significant dock score of 5g (−80.121 kcal/mol) in comparison with the standard ciprofloxacin (−88.263 kcal/mol) has been figured out upon molecular docking. [ABSTRACT FROM AUTHOR]

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Two series of novel substituted 1,4-dihydropyridine derivatives incorporating nitrogen mustard pharmacophore hybrids without spacer DHP-M (4a- 4d) and with ethyl spacer DHP-L-M (8a- 8g) were designed and synthesized. They were subjected to in silico ADME prediction study to check their drug-like properties and evaluated for their cytotoxicity against: A 549 (lung), COLO 205 (colon), U 87 (glioblastoma), and IMR-32 (neuroblastoma) human cancer cell lines in vitro using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay against chlorambucil and docetaxel. Majority of the test compounds exhibited moderate to significant cytotoxic activity. The highest activity in all the investigated cancer cells was displayed by DHP-M (4a). This may be due to the less steric hindrance offered by 4a. [ABSTRACT FROM AUTHOR]

A new series of 4-(4-substitutedbenzylideneamino)-5-((1-methyl-1 H-tetrazol-5-ylthio)methyl)-4 H-1,2,4-triazole-3-thiol derivatives ( 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k) are prepared using 4-amino-5-((1-methyl-1 H-tetrazol-5-ylthio)methyl-4 H-1,2,4-triazole-3-thiol ( 4), as an compound. The structures of all the newly synthesized products are established supported by their spectral 1H NMR, 13C NMR, FTIR, electrospray ionization (mass), and analytical data. All the compounds are screened for their insecticidal activity against Plodia interpunctella, and six compounds exhibited significant activity. [ABSTRACT FROM AUTHOR]

Coffee consists of several biological active compounds, such as caffeine, diterpenes, chlorogenic acids, and melanoidins, which may affect human health. The intake of each compound depends on the variety of coffee species, roasting degree, type of brewing method and serving size. The bioavailability and the distribution of each compound and its metabolites also contribute to coffee mechanisms of action. The health benefits of coffee consumption regarding cardiovascular system and metabolism mostly depend on its antioxidant compounds. In contrast, diterpenes and caffeine may produce harmful effects by raising lipid fraction and affecting endothelial function, respectively. Studying the mechanism of action of coffee components may help understanding weather coffee's impact on health is beneficial or hazardous. In this article, we reviewed the available information about coffee compounds and their mechanism of action. Furthermore, benefits and risks for cardiovascular system associated with coffee consumption will be discussed. [ABSTRACT FROM AUTHOR]

Using the chain-build-up method based on Empirical Conformational Energies of Peptides Program including solvation, we have computed, the low energy conformations of gonadotrpin-releasing hormone, GnRH, whose sequence is Pyro-Glu(PG)-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2. We have found 5,077 solvated conformations with conformational energies that were within 5 kcal/mole of that of the global minimum. These minima were found to occur in 802 distinct conformational classes of which 25 represented 70 % of the Boltzmann energy-weighted structures. Virtually all of these structures adopted bend conformations from Tyr 5-Leu 8, and 3,861 structures adopted bend conformations at residues 4-7. However, these structures differed significantly from one another, indicating that GnRH does not adopt a well-defined structure in aqueous solution consistent with the absence of a well-defined NMR structure of GnRH in water. A total of 300 of these structures were found to be superimposable on possible NMR structures for GnRH in DMSO with a combined statistical weight of 1.6 %. We found that Gly 6 adopts low energy 'starred' states, e.g., C* and D*, that are energetically forbidden to l-amino acids but are low energy for d-amino acids, with a statistical weight of 43 %. This can explain why substitutions of l-amino acids for Gly 6 are known to inactivate GnRH while d-amino acid substitutions enhance its activity. Using these findings, in the accompanying manuscript, we compute the low energy conformations for the substituted GnRHs that enable inference of possible receptor-bound conformations. [ABSTRACT FROM AUTHOR]

Ifosfamide (IFO) is an alkylating nitrogen mustard, administrated as an antineoplasmic agent. It is characterized by its intense urotoxic action, leading to hemorrhagic cystitis. This side effect of IFO raises the requirement for the co-administration with sodium 2-sulfanylethanesulfonate (Mesna) aiming to avoid or minimize this effect. IFO and Mesna were administrated separately on rabbit's lymphocytes in vivo, which were later developed in vitro. Cytogenetic markers for sister chromatid exchanges (SCEs), proliferation rate index (PRI) and Mitotic Index were recorded. Mesna's action, in conjunction with IFO reduces the frequency of SCEs, in comparison with the SCEs recordings obtained when IFO is administered alone. In addition to this, when high concentrations of Mesna were administered alone significant reductions of the PRI were noted, than with IFO acting at the same concentration on the lymphocytes. Mesna significantly reduces IFO's genotoxicity, while when administered in high concentrations it acts in an inhibitory fashion on the cytostatic action of the drug. [ABSTRACT FROM AUTHOR]

Curcumin (diferuloylmethane), the active ingredient in the eastern spice turmeric ( Curcuma longa), has been shown to inhibit the activities of numerous enzymes and signaling molecules involved in cancer, bacterial and viral infections and inflammatory diseases. We have investigated the inhibitory activities of curcumin and chemically modified curcumin (CMC) derivatives toward lethal factor (LF), the proteolytic component of anthrax toxin produced by the bacterium Bacillus anthracis. Curcumin (Compound 1) appears to inhibit the catalytic activity of LF through a mixture of inhibitory mechanisms, without significant compromise to the binding of oligopeptide substrates, and one CMC derivative in particular, Compound 3 (4-phenylaminocarbonylbis-demethoxycurcumin), is capable of inhibiting LF with potency comparable with the parent compound, while also showing improved solubility and stability. The quantitative reduction in catalytic activity achieved by the different CMC derivatives appears to be a function of the proportion of the multiple mechanisms through which they inhibit the enzyme. [ABSTRACT FROM AUTHOR]

An efficient, green, and chemoselective S-alkylation of 5-aryl-1H-1,2,4-triazole-3-thiones with diethyl (3-bromopropyl)phosphonate in water, catalyzed by nano-Fe2O3under ligand- and base-free conditions, is reported. Clean reaction, less expensive catalyst, excellent yields, and easy workup are the advantages of the present method. The catalyst can be easily collected by a magnet and recycled without significant loss in catalytic activity. The newly synthesized compounds were screened for their antioxidant property by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay. The majority of the compounds exhibited good antioxidant activity. [ABSTRACT FROM PUBLISHER]

In the present investigation, new hydrazinecarbothioamides 4-6 were synthesized by reaction of 4-(4-X-phenylsulfonyl)benzoic acids hydrazides (X= H, Cl, Br) 1-3 with 2,4-difluorophenyl isothiocyanate and further these were treated with sodium hydroxide to obtain 1,2,4-triazole-3-thione derivatives 7-9. The reaction of 7-9 with a-halogenated ketones, in basic media, afforded new S-alkylated derivatives 10-15. The structures of the synthesized compounds have been established on the basis of ¹H-NMR, 13C-NMR, IR, mass spectral studies and elemental analysis. The antioxidant activity of all compounds has been screened. Hydrazinecarbothioamides 4-6 showed excellent antioxidant activity and 1,2,4-triazole-3-thiones 7-9 showed good antioxidant activity using the DPPH method. [ABSTRACT FROM AUTHOR]

In the quest for potent antimicrobial agents, some new 1,3,4-thiadiazole derivatives ( 2- 11) were synthesized from the starting compound ( 1) 5-amino-1,3,4-thiadiazole-2(3H)-thione, with an aim to evaluate their antimicrobial effect on different pathogenic organisms isolated from microbial-infected cancer patients who had not yet received their radiation dose, compared to reference antibiotics. The titled compounds 5, 6, 10, and 11 were found to possess comparable or more potent activity than the reference compounds amikacin and sulperazone. Compound 5 was the most distinctive derivative identified in the present study because of its remarkable antibacterial activity exhibited against the Gram +ve strains, it has been scanned under electron microscope to determine the morphological changes that has taken place in the bacterial cells of Bacillus cereus and non-irradiated and irradiated Staphylococcus aureus. MIC of compound 5 and/or gamma irradiation affected the morphology of the tested strains causing; membrane damage, deformity on the surface of some cells, disappearance of the septum, elongation of some cells, and shortening of others. It may be hoped that the present study will encourage efforts toward the development of novel antibacterial agents that could be better in terms of efficacy and safety. [ABSTRACT FROM AUTHOR]

Herein, an excellent method for the synthesis of twelve novel Schiff base derivatives containing indole and triazole assisted by microwave irradiation is reported. Compared with the conventional method, the yields increased from 59–84 % to 85–96 % and the reaction time was reduced from 24–30 h to 4–8 min. Moreover, all series of the newly synthesized Schiff bases were evaluated for their antibacterial activity. The values of minimum inhibitory concentration (MIC) and IC50 indicated that many target compounds possessed excellent antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase-2 ( MMP-2) shares structural similarities with the angiotensin-converting enzyme ( ACE). ACE inhibitors have been described to inhibit MMP-2, but this inhibitory potential was not shown using a highly purified MMP-2. This study aimed to investigate the inhibitory potential of captopril and lisinopril regarding MMP-2 activity. The first objective was to test the potential of captopril to change the pH of the buffer solution. The second objective was to test the direct inhibitory effect of captopril and lisinopril on plasma MMP-2 and on recombinant human MMP-2 (rh MMP-2). The in vitro activity assays included gelatin zymography and a fluorimetric assay. Captopril solubilization significantly decreased the pH of the 50 mM Tris buffer solution at the following concentrations: 2 mM ( p < 0.05), 4 mM and 8 mM ( p < 0.01), while only the 8 mM lisinopril induced a drop in pH ( p < 0.05). Thus, only 200 mM buffer solutions were used. Zymography results of plasma MMP-2 and rh MMP-2 showed that inhibition only happened at captopril concentrations ≥ 4 and 1 mM, respectively ( p < 0.05), while only the higher concentration of lisinopril (8 mM) inhibited plasma MMP-2 ( p < 0.05). In the fluorimetric assay, captopril led to significant inhibition of the rhMMP-2 activity at concentrations ≥2 mM ( p < 0.01), whereas aminophenylmercuric acetate-activated rh MMP-2 was inhibited by 0.5 mM captopril ( p < 0.01). The captopril and lisinopril concentrations found to inhibit MMP-2 are 3 orders of magnitude higher than those present in vivo after drug administration. We also discuss possible pitfalls for gelatinase inhibitory assays (besides the obvious pH problem already cited). In conclusion, this study's data show that captopril and lisinopril did not inhibit MMP-2 directly at the concentrations reached in vivo. [ABSTRACT FROM AUTHOR]

This review describes the reactions of α/β-mercaptoalkanoic acids as building blocks for the synthesis of heterosteroids, polyfunctional heterocycles with pharmacological interest. Annelated heterocycles have been prepared by the cyclocondensation reaction of α- and β-mercaptoalkanoic acids with carbonyl compounds. This reaction takes place by nucleophilic addition, followed by cyclization with elimination of water. The main objective of this survey is to provide a comprehensive account of this reaction type in building various heterocycles, and examining their potential in developing better chemotherapeutic agents. [ABSTRACT FROM PUBLISHER]

A series of novel substituted aminobenzophenone derivatives containing nitrogen mustard moiety (5a- f) were synthesized and characterized on the basis of their IR, H NMR, C NMR, CHN, and mass spectral data. All the compounds when evaluated for chemical 4-(4-nitrobenzyl) pyridine alkylating activity proved to be active alkylating agents. All the synthesized compounds were subjected to physicochemical parameters determination required for central nervous system (CNS) activity through computational, online software, and QikProp 3.2. The log P values and other in silico ADME physicochemical descriptors analyzed lay between the ranges those are required for good BBB penetration. The in vitro antiproliferative activity against human cancer cell lines viz. A 549 (lung), COLO 205 (colon), U 87 (glioblastoma), and IMR-32 (neuroblastoma) was investigated. Most of the test compounds showed potent antitumor activity, especially compound (5f) which displayed the highest activity against CNS cancer cell line comparable to that of chlorambucil and docetaxel. The preliminary structure-activity relationship (SAR) revealed that 5-chloroaminobenzophenone-mustard series ( 5a-c) exhibited better antitumor activity than 5-nitroaminobenzophenone-mustard series (5d-f). [ABSTRACT FROM AUTHOR]

Every year, there are more than two lakhs of population affected with CNS tumor. Nitrogen mustard class of alkylating drugs, used clinically against various types of tumor, is too polar to cross the BBB. The redox chemical drug delivery prodrug approach is one of the most interesting procedures for delivering drugs in a sustained and specific manner to the CNS. The objective of the present study is to investigate the redox drug delivery system for the delivery of bis(2-chloroethyl)amine (nor mustard) as alkylating cytotoxic agent to the brain. Various redox derivatives of CDS-M ( 4a- d) were synthesized incorporating different alkyl/aryl moieties at ring nitrogen and subjected to in silico physicochemical parameters determination required for CNS activity through computational, online, and QikProp 3.2 software. The results of stability study, in vitro chemical (silver nitrate), and biological oxidation studies in human blood, rat blood, and brain homogenate for all CDS-M ( 4a- d) have been promising and suggest that brain targeting could be possible with more stable CDS-M ( 4d). The in vivo study showed that CDS-M ( 4d) was able to cross the BBB at detectable concentrations, and in vitro NBP alkylating activity of its quaternary salt ( 3d) was comparable to the known drug chlorambucil among all the synthesized derivatives. [ABSTRACT FROM AUTHOR]

Several new substituted sulfonamide compounds were synthesized and their structures were confirmed by 1H-NMR, 13C-NMR, FT-IR, and mass spectroscopy. The antibacterial activities of the synthesized compounds were screened against standard strains of six Gram positive and four Gram negative bacteria using the microbroth dilution assay. Most of the compounds studied showed promising activities against both types of bacteria. [ABSTRACT FROM AUTHOR]

ABSTRACT In the present study, new 1,2,4-triazoles, 1,3,4-thiadiazoles, and acylthiosemicarbaz-ides derived from 4-(4-chlorophenylsulfonyl)benzoic acid hydrazide were synthesized and screened for their antimicrobial and analgesic activities. Acylthiosemicarbazides 2-4 were synthesized by a reaction of 4-(4-chlorophenyl-sulfonyl)benzoic acid hydrazide 1 with different arylisothiocyanates.4,5-Disubstituted-2,4-dihydro-3H-1,2,4-triazol-3-thiones 5-7 and 2,5-disubstituted-1,3,4-thiadiazoles 8-10 were obtained by dehydrative cyclization of corresponding acylthiosemicarbazide derivatives 2-4 in basic media (8% aqueous sodium hydroxide) and in acidic media (sulfuric acid or phosphorous oxychloride), respectively. The structures of the newly synthesized compounds have been confirmed on the basis of elemental analysis and spectral studies (IR, 1H NMR, 13C NMR, MS). Their antimicrobial activities against some bacteria and yeasts were investigated. The analgesic activity of all compounds was performed with two pharmacological tests: the writhing test induced with acetic acid and hot-plate test. The results showed that triazole 7 had the best antimicrobial activity against Bacillus cereus. In the chemical stimulus test, triazoles 6 and 7 were the most active compounds whereas in the hot-plate test thiadiazoles 9 and 10 exhibited the highest analgesic activity. [ABSTRACT FROM AUTHOR]

Using pregnenolone and 7-deoxycholic acid as starting materials, some 17-acetamidoandrostane and N,N-dimethyl-7-deoxycholic amide derivatives were synthesized. The cytotoxicity of the synthesized compounds was tested in vitro against two tumor cell lines: SGC 7901 (human gastric carcinoma) and Bel 7404 (human liver carcinoma). The result showed that the blockage of the interaction of the amide group with outside groups might cause a decrease of the cytotoxicity, and an O-benzyloximino group at the 3-position of N,N-dimethyl-7-deoxycholic amide could enhance the cytotoxic activity of the compound. The information obtained from the studies provides the structure-activity relationship for these compounds and may be useful for the design of novel chemotherapeutic drugs. [ABSTRACT FROM AUTHOR]

A small focused chemical library constituted of sulfonamides was synthesized. These compounds were designed to lack the p-aminobenzene moiety typically found in sulfonamide antibiotics. Antimicrobial activities of these synthetic compounds were investigated against global predominant methicillin-resistant Staphylococcus aureus (MRSA) strain USA300 (SF8300) and control strains of Staphylococcus aureus ( S. aureus) ATCC 25923 and ATCC 29213 using disk diffusion and microdilution assays. Based on susceptibility results, potent S. aureus and MRSA USA300 growth inhibitors such as N-[3,5-bis(trifluoromethyl)phenyl]-4-bromobenzenesulfonamide with minimum inhibitory concentration (MIC) as low as 5.6 μg/cm along with other effective sulfonamides were discovered. Structure-activity correlations revealed that these desamino-benzenesulfonamides required electron-withdrawing substituents to be effective inhibitors of bacterial pathogen growth. In addition, their ability to inhibit growth of S. aureus strains was retained even when bacterial folate synthetic intermediate, p-aminobenzoic acid (PABA), was supplemented, whereas PABA supplementation completely diminished the antibacterial activity of the known sulfa drug tested, sulfamethoxazole. The sulfa-resistant MRSA strain COL also showed great susceptibility to these desamino-benzenesulfonamides. These results imply a unique mechanism of growth inhibition by these potent desamino-benzenesulfonamides, different from the well-known folate pathway target of sulfonamide antibiotics. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

No abstract is available for this article. [ABSTRACT FROM AUTHOR]

The thiophene-derived amido bis-nitrogen mustard N2, N2, N5, N5-tetrakis(2-chloroethyl)-3,4-dimethylthiophene-2,5-dicarboxamide was designed and synthesized via five-step reactions from commercially available 2-chloroacetonitrile. This target compound was confirmed by 1H NMR, 13C NMR, MS, IR spectra and elemental analyses, and its structure was further characterized by X-ray single-crystal analysis. The biological activities for the title compound and some intermediates were evaluated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that the title compound could inhibit efficiently the growth of the tested microorganisms including drug-resistant bacteria MRSA to some extent. Moreover, the target compound was found to be effective against prostatic carcinoma cell line (PC-3), breast carcinoma cell line (MCF-7), colon carcinoma (LoVo) and lung cancer (A549). Especially, it gave selective antitumor efficacy against prostatic carcinoma cell line (PC-3) at a low dose. [ABSTRACT FROM AUTHOR]

Novel 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazole-3-thiones bearing the pyrimidinylthio- moiety were synthesized by cyclization of a substituted-thiosemicarbazide precursor under different conditions. The thiosemicarbazide intermediates were easily accessed from reaction of biologically active 2-(4,6-dimethylpyrimidin-2-ylthio)acetohydrazide and 2-(2-dimethylamino-6-methyl pyrimidin-4-ylthio)acetohydrazide with cyclohexyl or phenyl isothiocyanate. The compounds are characterized by 1H, 13C NMR, IR spectroscopy and analytical data. [ABSTRACT FROM AUTHOR]