- LED 209 conjugated chitosan as a selective antimicrobial and potential anti-adhesion material
-
The rapid emergence of antibiotic-resistant Gram-negative bacteria (GNB) is becoming a global healthcare concern, and it urgently needs novel strategies to match the clinical challenge. In this work, we conjugated chitosan (CS) with LED 209, a highly selective inhibitor of QseC of GNB, to create the novel selective antimicrobial agent CS/LED. The data of FT-IR, NMR and elemental analysis for CS/LED conjugates proved the successful conjugation of CS with LED 209. Interestingly, the fluorescence signal detected in MDR-E. coli of CS/LED-FITC was about 2 times than that of CS-FITC at 3 h. The results shown that compared with CS, CS/LED exhibited higher selective antimicrobial on MDR-E. coli. Moreover, CS/LED exhibited the lower selectivity and cytotoxicity to mammalian cell than CS. Additionally, an unexpected enhancement of anti-adhesion activity against MDR-E. coli was determined by cellulose membrane coating CS/LED. The results demonstrated that CS/LED could reduce the adhesion of bacteria to the cellulose membrane by about 67.8%, while CS only reduced by about 45.3%. The dressings coated with CS/LED possessed the stronger ability to prevent microbial adhesion compared to the CS-coated dressing. Our present work firstly demonstrated that CS/LED had a highly selective activity and anti-adhesion activity against MDR-E. coli, which offered a potent and selective antimicrobial for combating multidrug-resistant GNB infections.
- Zhou, Zongbao,Chen, Tao,Mei, Naibin,Li, Bing,Xu, Zunkai,Wang, Lei,Wang, Xiaoying,Tang, Shunqing
-
-
Read Online
- Structures of silver sulfonamides
-
The structures of silver sulfonamides were found to depend highly on the substituent at the amide nitrogen of the sulfonamide. Silver is coordinated to that nitrogen and the sulfonamide is in the amido form if no substituent is present or if the substituent is a phenyl, acetyl, or 2-pyrimidyl group. If the substituent is a 2-thiazolyl or 2-pyridinyl group, the sulfonamide is in the imido form and silver coordinates to the nitrogen of the substituent. Depending on the number of suitable donor atoms per sulfonamide, the silver compounds are charged or uncharged and the primary amino group may be involved in complexation.
- Bult,Klasen
-
-
Read Online
- Discovery of N-(3,4-Dimethylphenyl)-4-(4-isobutyrylphenyl)-2,3,3a,4,5,9b-hexahydrofuro[3,2- c]quinoline-8-sulfonamide as a Potent Dual MDM2/XIAP Inhibitor
-
Murine double minute 2 (MDM2) and X-linked inhibitor of apoptosis protein (XIAP) are important cell survival proteins in tumor cells. As a dual MDM2/XIAP inhibitor reported previously, compound MX69 has low potency with an IC50 value of 7.5 μM against an acute lymphoblastic leukemia cell line EU-1. Herein, we report the structural optimization based on the MX69 scaffold, leading to the discovery of a 25-fold more potent analogue 14 (IC50 = 0.3 μM against EU-1). We demonstrate that 14 maintains its mode of action by dual targeting of MDM2 and XIAP through inducing MDM2 protein degradation and inhibiting XIAP mRNA translation, respectively, which resulted in cancer cell growth inhibition and cell death. The results strongly suggest that the scaffold based on 14 is promising for further optimization to develop a new therapeutic agent for leukemia and possibly other cancers where MDM2 and XIAP are dysregulated.
- Wu, Zhongzhi,Gu, Lubing,Zhang, Sicheng,Liu, Tao,Lukka, Pradeep B.,Meibohm, Bernd,Bollinger, John C.,Zhou, Muxiang,Li, Wei
-
p. 1930 - 1950
(2021/03/01)
-
- Structure-activity relationships of agonists for the orphan G protein-coupled receptor GPR27
-
GPR27 belongs, with GPR85 and GPR173, to a small subfamily of three receptors called “Super-Conserved Receptors Expressed in the Brain” (SREB). It has been postulated to participate in key physiological processes such as neuronal plasticity, energy metabolism, and pancreatic β-cell insulin secretion and regulation. Recently, we reported the first selective GPR27 agonist, 2,4-dichloro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (I, pEC50 6.34, Emax 100%). Here, we describe the synthesis and structure-activity relationships of a series of new derivatives and analogs of I. All products were evaluated for their ability to activate GPR27 in an arrestin recruitment assay. As a result, agonists were identified with a broad range of efficacies including partial and full agonists, showing higher efficacies than the lead compound I. The most potent agonist was 4-chloro-2,5-difluoro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7y, pEC50 6.85, Emax 37%), and the agonists with higher efficacies were 4-chloro-2-methyl-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7p, pEC50 6.04, Emax 123%), and 2-bromo-4-chloro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7r, pEC50 5.99, Emax 123%). Docking studies predicted the putative binding site and interactions of agonist 7p with GPR27. Selected potent agonists were found to be soluble and devoid of cellular toxicity within the range of their pharmacological activity. Therefore, they represent important new tools to further characterize the (patho)physiological roles of GPR27.
- Blavier, Jeremy,Charles, Ma?lle,Hanson, Julien,Kronenberger, Thales,Laschet, Céline,Müller, Christa E.,Pillaiyar, Thanigaimalai,Rosato, Francesca,Wozniak, Monika
-
-
- Comparative study between the anti-P. falciparum activity of triazolopyrimidine, pyrazolopyrimidine and quinoline derivatives and the identification of new PfDHODH inhibitors
-
In this work, we designed and synthesized 35 new triazolopyrimidine, pyrazolopyrimidine and quinoline derivatives as P. falciparum inhibitors (3D7 strain). Thirty compounds exhibited anti-P. falciparum activity, with IC50 values ranging from 0.030 to 9.1 μM. The [1,2,4]triazolo[1,5-a]pyrimidine derivatives were more potent than the pyrazolo[1,5-a]pyrimidine and quinoline analogues. Compounds 20, 21, 23 and 24 were the most potent inhibitors, with IC50 values in the range of 0.030–0.086 μM and were equipotent to chloroquine. In addition, the compounds were selective, showing no cytotoxic activity against the human hepatoma cell line HepG2. All [1,2,4]triazolo[1,5-a]pyrimidine derivatives inhibited PfDHODH activity in the low micromolar to low nanomolar range (IC50 values of 0.08–1.3 μM) and did not show significant inhibition against the HsDHODH homologue (0–30% at 50 μM). Molecular docking studies indicated the binding mode of [1,2,4]triazolo[1,5-a]pyrimidine derivatives to PfDHODH, and the highest interaction affinities for the PfDHODH enzyme were in agreement with the in vitro experimental evaluation. Thus, the most active compounds against P. falciparum parasites 20 (R = CF3, R1 = F; IC50 = 0.086 μM), 21 (R = CF3; R1 = CH3; IC50 = 0.032 μM), 23, (R = CF3, R1 = CF3; IC50 = 0.030 μM) and 24 (R = CF3, 2-naphthyl; IC50 = 0.050 μM) and the most active inhibitor against PfDHODH 19 (R = CF3, R1 = Cl; IC50 = 0.08 μM - PfDHODH) stood out as new lead compounds for antimalarial drug discovery. Their potent in vitro activity against P. falciparum and the selective inhibition of the PfDHODH enzyme strongly suggest that this is the mechanism of action underlying this series of new [1,2,4]triazolo[1,5-a]pyrimidine derivatives.
- Silveira, Flávia F.,de Souza, Juliana O.,Hoelz, Lucas V.B.,Campos, Vinícius R.,Jabor, Valquíria A.P.,Aguiar, Anna C.C.,Nonato, M. Cristina,Albuquerque, Magaly G.,Guido, Rafael V.C.,Boechat, Nubia,Pinheiro, Luiz C.S.
-
-
- Sulphonamidic Groups as Electron-Withdrawing Units in Ureido-Based Anion Receptors: Enhanced Anion Complexation versus Deprotonation
-
A sulphonamidic moiety was utilized as an electron-withdrawing group for enhancement of anion complexation features of urea-based receptors. A series of receptors varying in acidity of sulphonamidic and urea NH groups was synthesized and thoroughly tested. The individual complexation properties reflect deprotonation/complexation equilibrium in a given molecule as a function of the substitution. The receptors containing electron-donating groups in conjugation to the sulphonamidic moiety showed higher association constants towards H2PO4? and carboxylate anions, while those containing electron-withdrawing groups inclined to deprotonation of sulphonamidic NH. The deprotonation issue can be avoided by alkylation at the early step of receptor synthesis or it can be utilized for insertion of suitable groups that enable its anchoring on various substrates to form more elaborated receptor structures.
- ?imková, Ludmila,Císa?ová, Ivana,Cu?ínová, Petra,Ludvík, Ji?í,Sykora, Jan,Salvadori, Karolína
-
p. 1401 - 1411
(2020/08/05)
-
- Sequential C-S and S-N Coupling Approach to Sulfonamides
-
A one-pot three-component reaction involving nitroarenes, (hetero)arylboronic acids, and potassium pyrosulfite leading to sulfonamides was described. A broad range of sulfonamides bearing different reactive functional groups were obtained in good to excellent yields through sequential C-S and S-N coupling that does not require metal catalysts.
- Chen, Kai,Chen, Wei,Han, Bing,Chen, Wanzhi,Liu, Miaochang,Wu, Huayue
-
supporting information
p. 1841 - 1845
(2020/03/04)
-
- Discovery of secondary sulphonamides as IDO1 inhibitors with potent antitumour effects in vivo
-
Indoleamine 2,3-dioxygenase 1 (IDO1) as a key rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism plays an important role in tumour immune escape. Herein, a variety of secondary sulphonamides were synthesised and evaluated in the HeLa cell-based IDO1/kynurenine assay, leading to the identification of new IDO1 inhibitors. Among them, compounds 5d, 5l and 8g exhibited the strongest inhibitory effect with significantly improved activity over the hit compound BS-1. The in vitro results showed that these compounds could restore the T cell proliferation and inhibit the differentiation of na?ve CD4+ T cell into highly immunosuppressive FoxP3+ regulatory T (Treg) cell without affecting the viability of HeLa cells and the expression of IDO1 protein. Importantly, the pharmacodynamic assay showed that compound 5d possessed potent antitumour effect in both CT26 and B16F1 tumours bearing immunocompetent mice but not in immunodeficient mice. Functionally, subsequent experiments demonstrated that compound 5d could effectively inhibit tumour cell proliferation, induce apoptosis, up-regulate the expression of IFN-γ and granzyme B, and suppress FoxP3+ Treg cell differentiation, thereby activate the immune system. Thus, compound 5d could be a potential and efficacious agent for further evaluation.
- Ge, Shushan,Guo, Wenjie,Hu, Yue,Lai, Yisheng,Li, Yuezhen,Liu, Wen,Ma, Xuewei,Wang, Fang,Wang, Yan,Xu, Qiang,Zheng, Yingbo,Zhong, Haiqing,Zou, Yi
-
p. 1240 - 1257
(2020/06/18)
-
- Synthesis, structural, biological and in silico studies of new 5-arylidene-4-thiazolidinone derivatives as possible anticancer, antimicrobial and antitubercular agents
-
A new series of halogenated 4-thiazolidinone derivatives bearing the sulfonamide moiety was synthesized and characterized via FT-IR, 1H NMR, 13C NMR, HRMS and single crystal X-ray analysis. The newly synthesized target compounds were screened for their in vitro cytotoxicity on the HepG2 and MDA-MB-231 cell lines, and antimicrobial and antitubercular activity. The compounds showed promising anticancer activity towards the MDA-MB-231 cell line, and the trichloro derivatives with p-chloro substitution (6i) and p-hydroxy substitution (7e) exhibited excellent anticancer activity. Compounds 6b and 7c were observed to be moderate antimicrobial agents. The seven most potent anticancer agents were further studied for their antitubercular activity against an M. tuberculosis strain and it was found that compound 7e showed significant antitubercular activity. The potent candidates were also tested for hemolysis activity against human RBC cells and were found to be non-toxic. The mode of action for the observed anticancer activity was further supported by molecular docking studies of the potent compounds against the enzyme Aurora kinase (PDB ID: 4ZTR). Molecular dynamics (MD) simulations were further performed to study the stability of the ligand-protein complex.
- Sunil Kumar,Kudva, Jyothi,Bharath,Ananda,Sadashiva, Rajitha,Madan Kumar,Revanasiddappa,Kumar, Vasantha,Rekha,Naral, Damodara
-
p. 1597 - 1610
(2019/01/21)
-
- Effect of photodynamic antibacterial chemotherapy combined with antibiotics on Gram-positive and gram-negative bacteria
-
The well-known and rapidly growing phenomenon of bacterial resistance to antibiotics is caused by uncontrolled, excessive and inappropriate use of antibiotics. One of alternatives to antibiotics is Photodynamic Antibacterial Chemotherapy (PACT). In the present study, the effect of PACT using a photosensitizer Rose Bengal alone and in combination with antibiotics including methicillin and derivatives of sulfanilamide synthesized by us was tested against antibiotic-sensitive and antibiotic-resistant clinical isolates of Gram-positive S. aureus and Gram-negative P. aeruginosa. Antibiotic-sensitive and resistant strains of P. aeruginosa were eradicated by Rose Bengal under illumination and by sulfanilamide but were not inhibited by new sulfanilamide derivatives. No increase in sensitivity of P. aeruginosa cells to sulfanilamide was observed upon a combination of Rose Bengal and sulfanilamide under illumination. All tested S. aureus strains (MSSA and MRSA) were effectively inhibited by PACT. When treated with sub-MIC concentrations of Rose Bengal under illumination, the minimum inhibitory concentrations (MIC) of methicillin decreased significantly for MSSA and MRSA strains. In some cases, antibiotic sensitivity of resistant strains can be restored by combining antibiotics with PACT.
- Ilizirov, Yana,Formanovsky, Andrei,Mikhura, Irina,Paitan, Yossi,Nakonechny, Faina,Nisnevitch, Marina
-
-
- METHODS OF INHIBITING BACTERIAL VIRULENCE AND COMPOUNDS RELATING THERETO
-
The present invention relates to compounds and methods for the treatment of bacterial infections. Because their mechanism of action does not involve killing of bacteria or inhibiting their growth, the potential for these compounds to induce drug resistance in bacteria is minimized. Through inhibiting bacterial virulence, the present invention provides a novel means of treating bacterial infections.
- -
-
-
- Design, synthesis and biological evaluation of GPR55 agonists
-
GPR55, a G protein-coupled receptor, is an attractive target to alleviate inflammatory and neuropathic pain and treat osteoporosis and cancer. Identifying a potent and selective ligand will aid to further establish the specific physiological roles and pharmacology of the receptor. Towards this goal, a targeted library of 22 compounds was synthesized in a modular fashion to obtain structure-activity relationship information. The general route consisted of coupling a variety of p-aminophenyl sulfonamides to isothiocyanates to form acylthioureas. For the synthesis of a known naphthyl ethyl alcohol motif, route modification led to a shorter and more efficient process. The 22 analogues were analyzed for their ability to serve as agonists at GPR55 and valuable information for both ends of the molecule was ascertained.
- Fakhouri, Lara,Cook, Christopher D.,Al-Huniti, Mohammed H.,Console-Bram, Linda M.,Hurst, Dow P.,Spano, Michael B.S.,Nasrallah, Daniel J.,Caron, Marc G.,Barak, Larry S.,Reggio, Patricia H.,Abood, Mary E.,Croatt, Mitchell P.
-
p. 4355 - 4367
(2017/07/22)
-
- Design, synthesis, and evaluation of substituted nicotinamide adenine dinucleotide (NAD+) synthetase inhibitors as potential antitubercular agents
-
Nicotinamide adenine dinucleotide (NAD+) synthetase catalyzes the last step in NAD+ biosynthesis. Depletion of NAD+ is bactericidal for both active and dormant Mycobacterium tuberculosis (Mtb). By inhibiting NAD+ synthetase (NadE) from Mtb, we expect to eliminate NAD+ production which will result in cell death in both growing and nonreplicating Mtb. NadE inhibitors have been investigated against various pathogens, but few have been tested against Mtb. Here, we report on the expansion of a series of urea-sulfonamides, previously reported by Brouillette et al. Guided by docking studies, substituents on a terminal phenyl ring were varied to understand the structure–activity-relationships of substituents on this position. Compounds were tested as inhibitors of both recombinant Mtb NadE and Mtb whole cells. While the parent compound displayed very weak inhibition against Mtb NadE (IC50 = 1000 μM), we observed up to a 10-fold enhancement in potency after optimization. Replacement of the 3,4-dichloro group on the phenyl ring of the parent compound with 4-nitro yielded 4f, the most potent compound of the series with an IC50 value of 90 μM against Mtb NadE. Our modeling results show that these urea-sulfonamides potentially bind to the intramolecular ammonia tunnel, which transports ammonia from the glutaminase domain to the active site of the enzyme. This hypothesis is supported by data showing that, even when treated with potent inhibitors, NadE catalysis is restored when treated with exogenous ammonia. Most of these compounds also inhibited Mtb cell growth with MIC values of 19–100 μg/mL. These results improve our understanding of the SAR of the urea-sulfonamides, their mechanism of binding to the enzyme, and of Mtb NadE as a potential antitubercular drug target.
- Wang, Xu,Ahn, Yong-Mo,Lentscher, Adam G.,Lister, Julia S.,Brothers, Robert C.,Kneen, Malea M.,Gerratana, Barbara,Boshoff, Helena I.,Dowd, Cynthia S.
-
p. 4426 - 4430
(2017/09/12)
-
- Structure-based virtual screening and optimization of modulators targeting Hsp90-Cdc37 interaction
-
Identification of novel Hsp90 inhibitors to disrupt Hsp90-Cdc37 protein-protein interaction (PPI) could be an alternative strategy to achieve Hsp90 inhibition. In this paper, a series of small molecules targeting Hsp90-Cdc37 complex are addressed and characterized. The molecules' key characters are determined by utilizing a structure-based virtual screening workflow, derivatives synthesis, and biological evaluation. Structural optimization and structure–activity relationship (SAR) analysis were then carried out on the virtual hit of VS-8 with potent activity, which resulted in the discovery of compound 10 as a more potent regulator of Hsp90-Cdc37 interaction with a promising inhibitory effect (IC50?=?27?μM), a moderate binding capacity (KD?=?40?μM) and a preferable antiproliferative activity against several cancer lines including MCF-7, SKBR3 and A549?cell lines (IC50?=?26?μM, 15?μM and 38?μM respectively). All the data suggest that compound 10 exhibits moderate inhibitory effect on Hsp90-Cdc37 and could be regard as a first evidence of a non-natural compound targeting Hsp90-Cdc37 PPI.
- Wang, Lei,Li, Li,Zhou, Zi-Han,Jiang, Zheng-Yu,You, Qi-Dong,Xu, Xiao-Li
-
-
- Potent and selective N-(4-sulfamoylphenyl)thiourea-based GPR55 agonists
-
To date, many known G protein-coupled receptor 55 (GPR55) ligands are those identified among the cannabinoids. In order to further study the function of GPR55, new potent and selective ligands are needed. In this study, we utilized the screening results from PubChem bioassay AID 1961 which reports the results of Image-based HTS for Selective Agonists of GPR55. Three compounds, CID1792579, CID1252842 and CID1011163, were further evaluated and used as a starting point to create a series of nanomolar potency GPR55 agonists with N-(4-sulfamoylphenyl)thiourea scaffold. The GPR55 activity of the compounds were screened by using a commercial β-arrestin PathHunter assay and the potential compounds were further evaluated by using a recombinant HEK cell line exhibiting GPR55-mediated effects on calcium signalling. The designed compounds were not active when tested against various endocannabinoid targets (CB1R, CB2R, FAAH, MGL, ABHD6 and ABHD12), indicating compounds' selectivity for the GPR55. Finally, structure-activity relationships of these compounds were explored.
- Yrj?l?, Sari,Parkkari, Teija,Navia-Paldanius, Dina,Laitinen, Tuomo,Kaczor, Agnieszka A.,Kokkola, Tarja,Adusei-Mensah, Frank,Savinainen, Juha R.,Laitinen, Jarmo T.,Poso, Antti,Alexander, Amy,Penman, June,Stott, Lisa,Anskat, Marie,Irving, Andrew J.,Nevalainen, Tapio J.
-
p. 119 - 132
(2015/11/24)
-
- Iron-catalyzed N -arylsulfonamide formation through directly using nitroarenes as nitrogen sources
-
One-step, catalytic synthesis of N-arylsulfonamides via the construction of N-S bonds from the direct coupling of sodium arylsulfinates with nitroarenes was realized in the presence of FeCl2 and NaHSO3 under mild conditions. In this process, stable and readily available nitroarenes were used as nitrogen sources, and NaHSO3 acted as a reductant to provide N-arylsulfonamides in good to excellent yields. A broad range of functional groups were very well-tolerated in this reaction system. In addition, mechanistic studies indicated that the N-S bond might be generated through direct coupling of nitroarene with sodium arylsulfinate prior to the reduction of nitroarenes by NaHSO3. Accordingly, a reaction mechanism involving N-aryl-N-arenesulfonylhydroxylamine as an intermediate was proposed.
- Zhang, Weixi,Xie, Junyao,Rao, Bin,Luo, Meiming
-
p. 3504 - 3511
(2015/04/14)
-
- Synthesis and structure-activity relationship studies of 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives as potent and selective inhibitors of 12-lipoxygenase
-
Human lipoxygenases (LOXs) are a family of iron-containing enzymes which catalyze the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Our group has taken a particular interest in platelet-type 12-(S)-LOX (12-LOX) because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Herein, we report the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino) benzenesulfonamide-based scaffold. Top compounds, exemplified by 35 and 36, display nM potency against 12-LOX, excellent selectivity over related lipoxygenases and cyclooxygenases, and possess favorable ADME properties. In addition, both compounds inhibit PAR-4 induced aggregation and calcium mobilization in human platelets and reduce 12-HETE in β-cells.
- Luci, Diane K.,Jameson, J. Brian,Yasgar, Adam,Diaz, Giovanni,Joshi, Netra,Kantz, Auric,Markham, Kate,Perry, Steve,Kuhn, Norine,Yeung, Jennifer,Kerns, Edward H.,Schultz, Lena,Holinstat, Michael,Nadler, Jerry L.,Taylor-Fishwick, David A.,Jadhav, Ajit,Simeonov, Anton,Holman, Theodore R.,Maloney, David J.
-
p. 495 - 506
(2014/02/14)
-
- Synthesis, Characterization, Thermal and Antimicrobial studies of N-substituted Sulfanilamide derivatives
-
Four sulfanilamide derivatives N-[4-(phenylsulfamoyl)phenyl]acetamide (1), 4-amino-N-phenylbenzenesulfonamide (2), N-[4-(phenylsulfamoyl)phenyl]benzamide (3) and N-{4-[(3-chlorophenyl)sulfamoyl]phenylbenzamide (4) were synthesized and characterized by Infra-Red (IR), Nuclear Magnetic Resonance (NMR) and UV-visible (UV-Vis) spectra. Also Liquid Chromatographic (LCMS) and High Resolution Mass Spectrometric (HRMS) methods were used. Crystal structures of 1-4 were determined by single crystal X-ray diffraction (XRD) and their conformational and hydrogen bond (HB) network properties were examined with survey of the literature data. Compounds 1 and 2 crystallize in the same orthorhombic Pbca symmetry with equivalent molecular conformation (tilted V-shape) but showed distinct packing and hydrogen bonding models. Compounds 3 and 4 crystallize in monoclinic and triclinic crystal systems, albeit exhibiting identical molecular conformation (L-shaped). Same donor acceptor pairs both on 3 and 4 result to different kind of HB network. Thermogravimetric (TG) and differential scanning calorimetric (DSC) methods were used to evaluate thermal properties of the substances. All sulfanilamide derivatives have melting points between195-227 C, initiation of thermal decomposition between 259-271 C and enthalpies of fusion ΔHfusT = 38.96, 36.60, 46.23 and 44.81 kJ mol -1 were determined for 1-4, respectively. The derivatives were screened for their antibacterial and antifungal activities against various bacterial and fungal strains. It is observed that there is no significant antibacterial activity with the introduction of the benzene ring to CO-NH group or SO2-NH moiety, and none of the compounds exhibited antifungal activity.
- Lahtinen, Manu,Kudva, Jyothi,Hegde, Poornima,Bhat, Krishna,Kolehmainen, Erkki,Nonappa,Venkatesh,Naral, Damodara
-
p. 280 - 290
(2014/02/14)
-
- Nitrogen-containing polyhydroxylated aromatics as HIV-1 integrase inhibitors: Synthesis, structure-activity relationship analysis, and biological activity
-
Four series of forty-five nitrogen-containing polyhydroxylated aromatics based on caffeic acid phenethyl ester were designed and synthesized as HIV-1 integrase (IN) inhibitors. Most of these compounds inhibited IN catalytic activities in low micromolar range. Among these new analogues, compounds 9e and 9f were the most potent IN inhibitors with IC50 value of 0.7 μM against strand transfer reaction. Their key structure-activity relationships were also discussed.
- Yu, Shenghui,Zhang, Linna,Yan, Shifeng,Wang, Peng,Sanchez, Tino,Christ, Frauke,Debyser, Zeger,Neamati, Nouri,Zhao, Guisen
-
p. 628 - 640
(2012/10/29)
-
- Synthesis and biological evaluation of naphthoquinone analogs as a novel class of proteasome inhibitors
-
Screening of the NCI Diversity Set-1 identified PI-083 (NSC-45382) a proteasome inhibitor selective for cancer over normal cells. Focused libraries of novel compounds based on PI-083 chloronaphthoquinone and sulfonamide moieties were synthesized to gain a better understanding of the structure-activity relationship responsible for chymotrypsin-like proteasome inhibitory activity. This led to the demonstration that the chloronaphthoquinone and the sulfonamide moieties are critical for inhibitory activity. The pyridyl group in PI-083 can be replaced with other heterocyclic groups without significant loss of activity. Molecular modeling studies were also performed to explore the detailed interactions of PI-083 and its derivatives with the β5 and β6 subunits of the 20S proteasome. The refined model showed an H-bond interaction between the Asp-114 and the sulfonamide moiety of the PI-083 in the β6 subunit.
- Lawrence, Harshani R.,Kazi, Aslamuzzaman,Luo, Yunting,Kendig, Robert,Ge, Yiyu,Jain, Sanjula,Daniel, Kenyon,Santiago, Daniel,Guida, Wayne C.,Sebti, Said M.
-
experimental part
p. 5576 - 5592
(2010/09/15)
-
- Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu 4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)
-
Herein we disclose the synthesis and SAR of a series of 4-(phenylsulfamoyl)phenylacetamide compounds as mGlu4 positive allosteric modulators (PAMs) that were identified via a functional HTS. An iterative parallel approach to these compounds culminated in the discovery of VU0364439 (11) which represents the most potent (19.8 nM) mGlu4 PAM reported to date.
- Engers, Darren W.,Gentry, Patrick R.,Williams, Richard,Bolinger, Julie D.,Weaver, C. David,Menon, Usha N.,Conn, P. Jeffrey,Lindsley, Craig W.,Niswender, Colleen M.,Hopkins, Corey R.
-
scheme or table
p. 5175 - 5178
(2010/10/02)
-
- Pyridazine derivatives and related compounds, part 28.1 pyridazinesulfonamides: Synthesis and antimicrobial activity
-
The reaction of 3-chloropyridazine 1 with N -(un)Substituted 4-aminosulfonamides 3 gave the 3-substituted aminopyridazines 4. Also In addition, pyridazine-3-sulfonamides 7 were prepared from the reaction of pyridazine-3-sulfonylchloride 6 with different amines. All of these derivatives have been characterized by analytical and spectroscopic studies, and also were tested for their in vitro antibacterial and antifungal activity against a variety of microorganisms.
- El-Mariah, Fatma,Nassar, Ekhlass,Hosny, Mona,Deeb, Ali
-
experimental part
p. 92 - 102
(2009/04/16)
-
- Design and synthesis of novel nitrogen-containing polyhydroxylated aromatics as HIV-1 integrase inhibitors from caffeic acid phenethyl ester
-
A series of nitrogen-containing polyhydroxylated aromatics from caffeic acid phenethyl ester were designed and synthesized as HIV-1 integrase inhibitors. Most of these compounds exhibited potent inhibitory activities at micromolar concentrations against HIV-1 integrase in the 3′-end processing and the strand transfer. Their key structure-activity relationship was also discussed.
- Wang, Peng,Liu, Chuan,Sanches, Tino,Zhong, Yuan,Liu, Bo,Xiong, Junlong,Neamati, Nouri,Zhao, Guisen
-
supporting information; experimental part
p. 4574 - 4578
(2010/04/24)
-
- Analgesic agents without gastric damage: Design and synthesis of structurally simple benzenesulfonanilide-type cyclooxygenase-1-selective inhibitors
-
In order to create novel analgesic agents without gastric disturbance, structurally simple cyclooxygenase-1 (COX-1) inhibitors with a benzenesulfonanilide skeleton were designed and synthesized. As a result, compounds 11f and 15a, which possess a p-amino group on the benzenesulfonyl moiety and p-chloro group on the anilino moiety, showed COX-1-selective inhibition. Moreover compound 11f, which is the most potent compound in this study showed more potent analgesic activity than that of aspirin at 30 mg/kg by po. The anti-inflammatory activity and gastric damage, however, were very weak or not detectably different from aspirin. Since the structure of our COX-1 inhibitors are very simple, they may be useful as lead compounds for superior COX-1 inhibitors as analgesic agents without gastric disturbance.
- Zheng, Xiaoxia,Oda, Hiroyuki,Takamatsu, Kayo,Sugimoto, Yukio,Tai, Akihiro,Akaho, Eiichi,Ali, Hamed Ismail,Oshiki, Toshiyuki,Kakuta, Hiroki,Sasaki, Kenji
-
p. 1014 - 1021
(2007/10/03)
-
- Novel lead structures for antimalarial farnesyltransferase inhibitors
-
Through the combination of nitrophenylfurylacryloyl moiety which has been designed to occupy an aryl binding site of farnesyltransferase with several AA(X)-peptidomimetic substructures some novel farnesyltransferase inhibitors were obtained. Evaluation of their antimalarial activity and some initial modifications yielded a 4-benzophenone- and a sulfonamid-based novel lead for antimalarial farnesyltransferase inhibitors.
- Kettler,Sakowski,Wiesner,Ortmann,Jomaa,Schlitzer, Martin
-
p. 323 - 327
(2007/10/03)
-
- 4-Sulfonamidoanilide tertiary carbinols: A novel series of potassium channel openers
-
Sulfonamides are viable replacements for the phenylsulfonyl and benzoyl moieties initially described for the anilide tertiary carbinol series of K(ATP) potassium channel openers. The SAR of this new series and the synthetic chemistry employed to generate its members are described.
- Empfield,Mayhugh,Ohnmacht,Frank,Grant,Li
-
p. 775 - 778
(2007/10/03)
-
- Synthesis of 3-Methyl-1-Phenyl-5-Pyrazolones Containing Arylaminosulfonyl Groups
-
N-Aryl-substituted 3(4)-aminobenzenesulfonamides were synthesized.They are the starting compounds for the production of the corresponding substituted 3(4)-(3-methyl-5-oxo-2-pyrazolin-1-yl)-N-phenylbenzenesulfonamides.Data from the IR, PMR, and mass spectra are presented, and the fragmentation of the molecules is discussed.
- Lisitsyn, V. N.,Sazonchik, O. B.
-
p. 780 - 784
(2007/10/02)
-
- Process for formulating a synthetic drug for use in animal feed, and resulting formulation
-
A method of formulating a synthetic drug for use in animal feed, for the purpose of reducing carry-over of the synthetic drug to subsequent lots of animal feed in the feed mill.
- -
-
-
