scholarly journals SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF NEW 4H-PYRANO [3,2-h]QUINOLINES AND FUSED DERIVATIVES

2001 ◽  
Vol 69 (1) ◽  
pp. 33-52 ◽  
Author(s):  
H. Madkour ◽  
M. R. Mahmoud Mahmoud ◽  
A. Sakr ◽  
M. Habashy
Keyword(s):  
Antibacterial Activity ◽  
Hydrazine Hydrate ◽  
Carbon Disulfide ◽  
Cyano Group ◽  
Heterocyclic Ring ◽  
Structural Features ◽  
Nucleophilic Attack ◽  
Phenyl Isothiocyanate ◽  
E Coli ◽  
Carbon Nucleophiles

The starting materials, 2-amino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-pyran0[3,2-hlquinoline 1 and ethyl-2-amino-4-(3,4,5-trimethoxyphenyl)-4H-pyrano [3,2-hlquinolin-3-carboxylate 2 were synthesised from 8-hydroxyquinoline and a-cyano-3,4,5-trimethoxycinnamonitrileand/or ethyl-a-cyano-3,4,5-trimethoxy-cinnamatre respectively. In order to construct a third heterocyclic ring 1 and 2were condensed with ethyl bromoacetate, formarnide, carbon disulfide to afford pyrrolo-, pyrimido- and thiazinopyranoquinolines 3-6respectively. The S-alkylated products 7 and 8 were obtained by the effect of chloroacetonitrile and/or ethyl chloroacetate on thiazinopyranoquinoline derivative 6. The attempt of cyanomethylation of the amino functional group of 1 to yield 10 with chloroacetonitrile in AcOHIAcONa failed and instead, pyridopyranoquinoline derivative 9 was obtained which is visualized to occur via cyclization of the initially formed acetylarnino derivative by nucleophilic attack on the cyano group. Acetylation of 1 and 2 with acetic anhydride afforded the mono- and di-acetyl derivatives 11a and 11b respectively. A plausible explanation to form the mono-derivative with 1 and the di-derivative with 2 is the higher deactivating effect of the cyano function over that of the carboxyethyl group. Furoylation of 1 and 2 was achieved by furoyl chloride to give 12a and 12b respectively. The structural features of pyranoquinoline 2 were inferred from its microanalysis and spectral data such as IR,1H-NMR and MS as well as its chemical reactions, as a bifunctional compound with carbon nucleophiles namely, phenyl isothiocyanate and nitrogen nucleophilic species namely, p-toluidine, benzylamine, aniline and hydrazine hydrate to give pyrimidopyranoquinoline derivative 13, carboxamides 14a-c and carboxyhydrazide 15 respectively. When the hydrazide 15 was treated with carbon disulfide inpresence of KOH, it afforded the potassium salt 16 which was submitted to react with hydrazine hydrate at room temperature to give 17. The hydrazido group of 15was utilized to construct heterocyclic moieties attached to postion-3 of the pyranoquinoline structure. Thus, the reaction of the carboxyhydrazide15 with phenyl isothiocyanate, acetylacetone, and benzoylacetone resulted in the formation of 18, 19a and 19b respectively. Ethyl carbazate as a typical mesophile reacted with 2 to afford a fused tetracyclic product triazepinopyranoquinoline 20 via cyclization of the initially formed hydrazide. Among sixteen compounds screened against E. coli and S. aureus respectively,compounds 2 and 14c show a high order of antibacterial activity against both bacteria. 12b is strongly potent against Staphylococcus aureus.

scholarly journals Peptide/Peptoid Hybrid Oligomers: The Influence of Hydrophobicity and Relative Side-Chain Length on Antibacterial Activity and Cell Selectivity

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4429 ◽  
Author(s):  
Nicki Frederiksen ◽  
Paul R. Hansen ◽  
Fredrik Björkling ◽  
Henrik Franzyk
Keyword(s):  
Antibacterial Activity ◽  
Chain Length ◽  
Hydrophobic Surface ◽  
Structural Features ◽  
Side Chain ◽  
Side Chains ◽  
Side Chain Length ◽  
E Coli ◽  
Cell Selectivity ◽  
Wide Range

Previous optimisation studies of peptide/peptoid hybrids typically comprise comparison of structurally related analogues displaying different oligomer length and diverse side chains. The present work concerns a systematically constructed series of 16 closely related 12-mer oligomers with an alternating cationic/hydrophobic design, representing a wide range of hydrophobicity and differences in relative side-chain lengths. The aim was to explore and rationalise the structure–activity relationships within a subclass of oligomers displaying variation of three structural features: (i) cationic side-chain length, (ii) hydrophobic side-chain length, and (iii) type of residue that is of a flexible peptoid nature. Increased side-chain length of cationic residues led to reduced hydrophobicity till the side chains became more extended than the aromatic/hydrophobic side chains, at which point hydrophobicity increased slightly. Evaluation of antibacterial activity revealed that analogues with lowest hydrophobicity exhibited reduced activity against E. coli, while oligomers with the shortest cationic side chains were most potent against P. aeruginosa. Thus, membrane-disruptive interaction with P. aeruginosa appears to be promoted by a hydrophobic surface of the oligomers (comprised of the aromatic groups shielding the cationic side chains). Peptidomimetics with short cationic side chains exhibit increased hemolytic properties as well as give rise to decreased HepG2 (hepatoblastoma G2 cell line) cell viability. An optimal hydrophobicity window could be defined by a threshold of minimal hydrophobicity conferring activity toward E. coli and a threshold for maximal hydrophobicity, beyond which cell selectivity was lost.

Concise Synthesis and Displacement Reactions of Model 3-(Alkylthio)- 6-chloro- and 2,6-Dichlorothieno[2,3-e][1,4,2]dithiazine 1,1-Dioxides

2011 ◽  
Vol 66 (7) ◽  
pp. 715-720
Author(s):  
Rajab Abu-El-Halawa ◽  
Mohanad Masad ◽  
Yaser Bathich ◽  
Mahmoud Al-Refai ◽  
Mohammad M. Ibrahim ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Carbon Disulfide ◽  
Dimethyl Sulfate ◽  
Alkyl Halides ◽  
Sulfuryl Chloride ◽  
Molar Ratio ◽  
New Approach ◽  
E Coli ◽  
Displacement Reactions

A series of 3-(alkylthio)-6-chlorothieno[2,3-e][1,4,2]dithiazine 1,1-dioxides (7a - e) were prepared via interaction of deprotonated 2,5-dichlorothiophene-3-sulfonamide with carbon disulfide under reflux, followed by alkylation with alkyl halides. Employment of dimethyl sulfate afforded the isomeric 2-methyl-3-thione derivative 8 together with the expected 3-(methylthio) derivative 7a in a molar ratio of 1 : 4. Treatment of 7a or 10 with ethylamine, aniline or p-chloroaniline produced the corresponding N-ethyl- (or N-phenyl)-6-chlorothieno[2,3-e][1,4,2]dithiazine-3-amine 1,1-dioxides 3a - c. Likewise, interaction of 7a with methylhydrazine (or phenylhydrazine) gave the respective 3-(1-methylhydrazinyl or 2-phenylhydrazinyl) 1,1-dioxides 9a, b. Desulfonation of 6-chloro-3-(methylthio)thieno[ 2,3-e][1,4,2]dithiazine 1,1-dioxide (7a) with sulfuryl chloride produced 3,6-dichlorothieno[2,3- e][1,4,2]dithiazine 1,1-dioxide (10). The latter compound was used as a substrate for the preparation of N-alkyl- (or aryl)-6-chlorothieno[2,3-e][1,4,2]dithiazin-3-amine 1,1-dioxides 3a - c representing a new approach for the synthesis of similar derivatives. Compounds 7a - e showed modest to low antibacterial activity against E. coli and S. aureus.

scholarly journals SYNTHESIS AND UTILITY OF NEW POLYCYCLIC COMPOUNDS AS POTENTIAL ANTIMICROBIALS BASED ON CHROMENE MOIETY

2019 ◽  
pp. 49-56
Author(s):  
MAHMOUD N. ABDELAZIZ ◽  
EMAN S. ZARIE ◽  
ALAADIN E. SARHAN
Keyword(s):  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Condensation Reaction ◽  
Ethyl Cyanoacetate ◽  
Inhibition Zone ◽  
Phenyl Isothiocyanate ◽  
Polycyclic Compounds ◽  
E Coli ◽  
Multiple Species

Objective: The present research aims to synthesize some new polycyclic compounds including chromene moiety and study their antimicrobial activity. Methods: Several new polycyclic systems including chromene scaffold incorporated with pyridine, pyrimidine, imidazopyrimidine, and imidazodiazocine were achieved via condensation reaction of chromene derivative under the proper condition with various reagents namely; cyanothioacetamide, phenyl isothiocyanate, malononitrile, carbon disulfide, benzaldehyde, triethylorthoformate, and 1,4-dichlorobutane. Moreover, a chlorodiazenyl chromene derivative was reacted with some substances possessing active–CH2-bridge such as ethyl cyanoacetate and malononitrile to end up with hydrazono compounds. Such compounds were eventually cyclized with hydrazine hydrate to form pyrazole and oxopyrazole derivatives. Moreover, compound 1 was treated with benzoyl acetone, and then followed by cyclization with malononitrile to provide the corresponding 2-amino14-(4-methoxyphenyl)-4-methy-5-phenyl-14H-benzo[5,6] chromeno[2,3H][1,6]naphthyridine-3-carbonitrile (20). Results: The results of the antimicrobial screening in vitro revealed that the inhibition zone (mm) of the synthesized compounds 1-3, 5 and 8 implied their optimum antibacterial activity, while the compounds 4, 6 and 9-13, 15 showed a moderate to weak antibacterial activity against multiple species of B. subtilis, S. aureus, E. coli and P. aeruginosa. In contrast, the compounds 1, 6, 11, 15 showed high antifungal activities against different species of A. flavinand C. albicans, while the other compounds exhibit a moderate to poor antifungal activity. Conclusion: It is remarkable that a series of chromene derivatives synthesized by a simple and available method leads to a molecule of promising antimicrobial activity. Further research is recommended to approve the importance of polycyclic systems for various applications.

Heterocyclic Variants of the Purine System. II. Derivatives of Thiazolo[4,5-E]-1,2,4-Triazines, a New Heterocyclic Ring System

1987 ◽  
Vol 40 (4) ◽  
pp. 693 ◽  
Author(s):  
NW Jacobsen ◽  
AE Philippides
Keyword(s):  
Carbon Disulfide ◽  
Heterocyclic Ring ◽  
Ring System ◽  
Phenyl Isothiocyanate ◽  
Triazine Ring ◽  
Phosphorus Pentasulfide ◽  
Derivatives Of

.Some representative derivatives of the new thiazolo [4,5- e]-1,2,4-triazine ring system were prepared from 5-acylamino-1,2,4-triazin-6(1 H)-ones by heating with phosphorus pentasulfide in pyridine. Further derivatives of the biheterocyclo system were also made from 6-methylthio-1,2,4-triazin-5-amines by heating with carbon disulfide or phenyl isothiocyanate.

Antibacterial Activity of Thujaoccidentalis,ThujaorientalisandChamaecyparisobtusa

2017 ◽  
Vol 8 (03) ◽  
Author(s):  
Kyoung- Sun Seo ◽  
Seong Woo Jin ◽  
Seongkyu Choi ◽  
Kyeong Won Yun
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Antibacterial Agent ◽  
Methanol Extract ◽  
The Other ◽  
Diffusion Method ◽  
E Coli ◽  
Agar Diffusion ◽  
Agar Diffusion Method ◽  
Crude Methanol Extract

The antibacterial activity of three Cupressaceae plants (Thujaoccidentalis,ThujaorientalisandChamaecyparisobtusa) was tested against three bacteria using the agar diffusion method. The ether and ethylacetate fraction of crude methanol extract from the three plants showed potent antibacterial activity against the tested microorganisms. The result showed that Staphylococcus aureus revealed the most sensitivity among the tested bacteria. Thujaoccidentalisether fraction and Thujaorientalis hexane fraction exhibited the highest antibacterial activity against Staphylococcus aureus. E. coli was shown the highest MIC values compared to the other two tested bacteria, which indicates the lowest antibacterial activity against the bacterium. This study promises an interesting future for designing a potentially active antibacterial agent from the three Cupressaceae plants.

Bioenhancing Effect of Cow Urine Distillate and Pepper Extract on Antibacterial Activity of Azadirachta Indica Leaves

1970 ◽  
Vol 9 (2) ◽  
pp. 3212-3214
Author(s):  
Pramod Dhakal ◽  
Ankit a Achary ◽  
Vedamurthy Joshi
Keyword(s):  
Antibacterial Activity ◽  
Azadirachta Indica ◽  
Pathogenic Bacteria ◽  
Ethanol Extract ◽  
Watery Diarrhea ◽  
Diffusion Method ◽  
E Coli ◽  
Drug Molecules ◽  
Cow Urine

Bioenhancers are drug facilitator which do not show the typical drug activity but in combination to enhance the activity of other molecule in several way including increase the bioavailability of drug across the membrane, potentiating the drug molecules by conformational interaction, acting as receptor for drug molecules and making target cell more receptive to drugs and promote and increase the bioactivity or bioavailability or the uptake of drugs in combination therapy. The objective of the present study was to evaluate the antibacterial and activity of combination in Azadirachta indica extract with cow urine distillate and pepper extract against common pathogenic bacteria, a causative agent of watery diarrhea. It has been found that Indian indigenous cow urine and its distillate also possess bioenhancing ability. Bioenhancing role of cow urine distillate (CUD) and pepper extract was investigated on antibacterial activity of ethanol extract of Azadirachta indica. Antibacterial activity of ethanol extract neem alone and in combination with CUD and pepper extract were determined the ATCC strains against Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and E-coli by cup plate diffusion method. Ethanol extract of neem has showed more effect on P. aeruginosa, E-coli than S. aureus and K. pneumonia with combination of CUD and pepper extract. CUD and pepper did not show any inhibition of test bacteria in low concentration. The antibacterial effect of combination of extract and CUD was higher than the inhibition caused by extract alone and is suggestive of the bioenhancing role of cow urine distillate and pepper. Moreover, inhibition of test bacteria was observed with less concentration of extract on combining with CUD

Identification of N-Substituted Triazolo-azetidines as Novel Antibacterials using pDualrep2 HTS Platform

2019 ◽  
Vol 22 (5) ◽  
pp. 346-354
Author(s):  
Yan A. Ivanenkov ◽  
Renat S. Yamidanov ◽  
Ilya A. Osterman ◽  
Petr V. Sergiev ◽  
Vladimir A. Aladinskiy ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Large Scale ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
Reporter System ◽  
E Coli ◽  
Starting Point ◽  
High Concentrations ◽  
Mic Value

Aim and Objective: Antibiotic resistance is a serious constraint to the development of new effective antibacterials. Therefore, the discovery of the new antibacterials remains one of the main challenges in modern medicinal chemistry. This study was undertaken to identify novel molecules with antibacterial activity. Materials and Methods: Using our unique double-reporter system, in-house large-scale HTS campaign was conducted for the identification of antibacterial potency of small-molecule compounds. The construction allows us to visually assess the underlying mechanism of action. After the initial HTS and rescreen procedure, luciferase assay, C14-test, determination of MIC value and PrestoBlue test were carried out. Results: HTS rounds and rescreen campaign have revealed the antibacterial activity of a series of Nsubstituted triazolo-azetidines and their isosteric derivatives that has not been reported previously. Primary hit-molecule demonstrated a MIC value of 12.5 µg/mL against E. coli Δ tolC with signs of translation blockage and no SOS-response. Translation inhibition (26%, luciferase assay) was achieved at high concentrations up to 160 µg/mL, while no activity was found using C14-test. The compound did not demonstrate cytotoxicity in the PrestoBlue assay against a panel of eukaryotic cells. Within a series of direct structural analogues bearing the same or bioisosteric scaffold, compound 2 was found to have an improved antibacterial potency (MIC=6.25 µg/mL) close to Erythromycin (MIC=2.5-5 µg/mL) against the same strain. In contrast to the parent hit, this compound was more active and selective, and provided a robust IP position. Conclusion: N-substituted triazolo-azetidine scaffold may be used as a versatile starting point for the development of novel active and selective antibacterial compounds.

Microwave assisted synthesis of novel Pyrazole derivatives and their biological evaluation as anti-bacterial agents

2020 ◽  
Vol 23 ◽  
Author(s):  
Hadis Khodadad ◽  
Farhad Hatamjafari ◽  
Khalil Pourshamsian ◽  
Babak Sadeghi
Keyword(s):  
Antibacterial Activity ◽  
Aromatic Aldehydes ◽  
Catalytic Amount ◽  
Antibacterial Activities ◽  
Structural Features ◽  
Biological Evaluation ◽  
Aureus Strain ◽  
Microwave Assisted Synthesis ◽  
Pyrazole Derivatives ◽  
Microwave Assisted

Aim and Objective: Microwave-assisted condensation of acetophenone 1 and aromatic aldehydes 2 gave chalcone analogs 3, which were cyclized to pyrazole derivatives 6a-f via the reaction with hydrazine hydrate and oxalic acid in the presence of the catalytic amount of acetic acid in ethanol. Materials and Methods: The structural features of the synthesized compounds were characterized by melting point, FT-IR, 1H, 13C NMR and elemental analysis. Results: The antibacterial activities of the synthesized pyrazoles was evaluated against three gram-positive bacteria such as Enterococcus durans, Staphylococcus aureus, Bacillus subtilis and two gram-negative bacteria such as Escherichia coli and Salmonella typhimurium. Conclusion: All the synthesized pyrazoles showed relatively high antibacterial activity against S. aureus strain and none of them demonstrated antibacterial activity against E. coli.

Large-scale High-throughput Screening Revealed 5'-(carbonylamino)-2,3'- bithiophene-4'-carboxylate as Novel Template for Antibacterial Agents

2020 ◽  
Vol 17 (5) ◽  
pp. 716-724
Author(s):  
Yan A. Ivanenkov ◽  
Renat S. Yamidanov ◽  
Ilya A. Osterman ◽  
Petr V. Sergiev ◽  
Vladimir A. Aladinskiy ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
High Throughput ◽  
High Throughput Screening ◽  
Large Scale ◽  
Antibacterial Agents ◽  
Sos Response ◽  
Luciferase Assay ◽  
Translational Machinery ◽  
E Coli ◽  
New Class

Background: The key issue in the development of novel antimicrobials is a rapid expansion of new bacterial strains resistant to current antibiotics. Indeed, World Health Organization has reported that bacteria commonly causing infections in hospitals and in the community, e.g. E. Coli, K. pneumoniae and S. aureus, have high resistance vs the last generations of cephalosporins, carbapenems and fluoroquinolones. During the past decades, only few successful efforts to develop and launch new antibacterial medications have been performed. This study aims to identify new class of antibacterial agents using novel high-throughput screening technique. Methods: We have designed library containing 125K compounds not similar in structure (Tanimoto coeff.< 0.7) to that published previously as antibiotics. The HTS platform based on double reporter system pDualrep2 was used to distinguish between molecules able to block translational machinery or induce SOS-response in a model E. coli system. MICs for most active chemicals in LB and M9 medium were determined using broth microdilution assay. Results: In an attempt to discover novel classes of antibacterials, we performed HTS of a large-scale small molecule library using our unique screening platform. This approach permitted us to quickly and robustly evaluate a lot of compounds as well as to determine the mechanism of action in the case of compounds being either translational machinery inhibitors or DNA-damaging agents/replication blockers. HTS has resulted in several new structural classes of molecules exhibiting an attractive antibacterial activity. Herein, we report as promising antibacterials. Two most active compounds from this series showed MIC value of 1.2 (5) and 1.8 μg/mL (6) and good selectivity index. Compound 6 caused RFP induction and low SOS response. In vitro luciferase assay has revealed that it is able to slightly inhibit protein biosynthesis. Compound 5 was tested on several archival strains and exhibited slight activity against gram-negative bacteria and outstanding activity against S. aureus. The key structural requirements for antibacterial potency were also explored. We found, that the unsubstituted carboxylic group is crucial for antibacterial activity as well as the presence of bulky hydrophobic substituents at phenyl fragment. Conclusion: The obtained results provide a solid background for further characterization of the 5'- (carbonylamino)-2,3'-bithiophene-4'-carboxylate derivatives discussed herein as new class of antibacterials and their optimization campaign.

Structure-Activity Relationship and Antimicrobial Evaluation of N-Phenylpyrazole Curcumin Derivatives

2020 ◽  
Vol 16 (4) ◽  
pp. 481-488
Author(s):  
Heli Sanghvi ◽  
Satyendra Mishra
Keyword(s):  
Antibacterial Activity ◽  
Gram Negative Bacteria ◽  
Pyrazole Derivatives ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
Curcumin Derivatives ◽  
Structure Activity ◽  
Electron Donating Groups ◽  
Derivatives Of

Background: Curcumin, one of the most important pharmacologically significant natural products, has gained significant consideration among scientists for decades since its multipharmacological activities. 1, 3-Dicarbonyl moiety of curcumin was found to be accountable for the rapid degradation of curcumin molecule. The aim of present work is to replace 1, 3-dicarbonyl moiety of curcumin by pyrazole and phenylpyrazole derivatives with a view to improving its stability and to investigate the role of substitution in N-phenylpyrazole curcumin on its antibacterial activity against both Gram-positive as well as Gram-negative bacteria. Methods: Pyrazole derivatives of curcumin were prepared by heating curcumin with phenyhydrazine/ substituted phenyhydrazine derivatives in AcOH. The residue was purified by silica gel column chromatography. Structures of purified compounds were confirmed by 1H NMR and Mass spectroscopy. The synthesized compounds were evaluated for their antibacterial activity by the microdilution broth susceptibility test method against gram positive (S. aureus) and gram negative (E. coli). Results: Effects of substitution in N-phenylpyrazole curcumin derivatives against S. aureus and E. coli were studied. The most active N-(3-Nitrophenylpyrazole) curcumin (12) exhibits twenty-fold more potency against S. aureus (MIC: 10μg/mL)) and N-(2-Fluoroophenylpyrazole) curcumin (5) fivefold more potency against E. coli (MIC; 50 μg/mL) than N-phenylpyrazole curcumin (4). Whereas, a remarkable decline in anti-bacterial activity against S. aureus and E. coli was observed when electron donating groups were incorporated in N-phenylpyrazole curcumin (4). Comparative studies of synthesized compounds suggest the effects of electron withdrawing and electron donating groups on unsubstituted phenylpyrazole curcumin (4). Conclusion: The structure-activity relationship (SAR) results indicated that the electron withdrawing and electron donating at N-phenylpyrazole curcumin played key roles for their bacterial inhibitory effects. The results of the antibacterial evaluation showed that the synthesized pyrazole derivatives of curcumin displayed moderate to very high activity in S. aureus. In conclusion, the series of novel curcumin derivatives were designed, synthesized and tested for their antibacterial activities against S. aureus and E. coli. Among them, N-(3-Nitrophenylpyrazole curcumin; 12) was most active against S. aureus (Gram-positive) and N-(2-Fluoroophenylpyrazole) curcumin (5) against E. coli (Gram-negative) bacteria.

Sign in / Sign up

Export Citation Format

Share Document