39 results on '"El-Sayed E. Habib"'
Search Results
2. Synthesis and in vitro antibacterial, antifungal, anti-proliferative activities of novel adamantane-containing thiazole compounds
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Eman T. Warda, Mahmoud B. El-Ashmawy, El-Sayed E. Habib, Mohammed S. M. Abdelbaky, Santiago Garcia-Granda, Subbiah Thamotharan, Ali A. El-Emam, Science, Technology & Innovation Funding Authority, and Egyptian Knowledge Bank
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Multidisciplinary - Abstract
A series of (Z)-N-(adamantan-1-yl)-3,4-diarylthiazol-2(3H)-imines (5a-r) was synthesized via condensation of 1-(adamantan-1-yl)-3-arylthioureas (3a-c) with various aryl bromomethyl ketones (4a-f). The structures of the synthesized compounds were characterized by H NMR, C NMR and by X-ray crystallography. The in vitro inhibitory activities of the synthesized compounds were assessed against a panel of Gram-positive and Gram-negative bacteria, and pathogenic fungi. Compounds 5c, 5g, 5l, 5m, and 5q displayed potent broad-spectrum antibacterial activity, while compounds 5a and 5o showed activity against the tested Gram-positive bacteria. Compounds 5b, 5l and 5q displayed potent antifungal activity against Candida albicans. In addition, the synthesized compounds were evaluated for anti-proliferative activity towards five human tumor cell lines. The optimal anti-proliferative activity was attained by compounds 5e and 5k which showed potent inhibitory activity against all the tested cell lines. Molecular docking analysis reveals that compounds 5e and 5k can occupy the positions of NAD cofactor and the histone deacetylase inhibitor EX527 at the active site of SIRT1 enzyme., Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).
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- 2022
3. Synthesis and in vitro antibacterial, antifungal, anti-proliferative activities of novel adamantane-containing thiazole compounds
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Eman T, Warda, Mahmoud B, El-Ashmawy, El-Sayed E, Habib, Mohammed S M, Abdelbaky, Santiago, Garcia-Granda, Subbiah, Thamotharan, and Ali A, El-Emam
- Abstract
A series of (Z)-N-(adamantan-1-yl)-3,4-diarylthiazol-2(3H)-imines (5a-r) was synthesized via condensation of 1-(adamantan-1-yl)-3-arylthioureas (3a-c) with various aryl bromomethyl ketones (4a-f). The structures of the synthesized compounds were characterized by
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- 2022
4. Antimicrobial efficacy of extracts of Saudi Arabian desert
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Hani M J, Khojah, Osama B, Abdelhalim, Mahmoud A H, Mostafa, and El-Sayed E, Habib
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We sought to investigate theDry extracts were prepared using methanol, ethyl acetate, and distilled water, while the latter was used for preparing fresh extracts. The extracts were microbiologically evaluated through the disc-diffusion agar method; the zones of inhibition of microbial growth were measured post-incubation. The minimum bactericidal concentration (MBC) and minimum inhibitory concentration (MIC) were determined in Müller-Hinton Broth through the microdilution susceptibility method. anti-biofilm activity was assessed for potent extracts.Dry extracts showed potent activity (16-mm inhibition zones) against gram-positive (
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- 2022
5. Physico-Chemical and Microbiological Study for the Stability of Phenytoin Sodium Extemporaneously Compounded Suspension in Saudi Arabia Hospitals
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Yaser M. Alahmadi, Sameh Ahmed, Abdulelah Alhusayni, Abdulmalik Alqurshi, Syed Ata ur Rahman, Abdullah Alsaedi, El-Sayed E. Habib, Alaa Omer M. Abdullaal, and Badr Ahmed A. Taher
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Phenytoin ,medicine.medical_specialty ,Relative scarcity ,partial seizures ,business.industry ,medicine.disease ,Suspension (chemistry) ,Phenytoin Sodium ,Age groups ,medicine ,Physical stability ,Intensive care medicine ,business ,medicine.drug - Abstract
Epilepsy is a chronic and the fourth most common neurological disorder which affects people of all age groups. Recently research and awareness on epilepsy-related deaths have rapidly grown over the past two decades. Many previous studies are attributed to the guidelines that apprise health care professionals in handling these deaths, but there is a relative scarcity of information accessible for clinicians and pharmacists who are responsible for manufacturing or preparing the extemporaneous anti-epileptic suspensions in the hospitals. Mostly in partial seizures, phenytoin is one of the first-choice drugs. In Saudi Arabian hospitals, the extemporaneous preparation of phenytoin suspension is common, but the hot climatic weather in Saudi Arabia possesses stability problems that should be tackled as the prepared suspension should pass all the stability tests to ensure uniform dosage of the extemporaneous formulation. In the current study, the commercial capsules were used to prepare the oral phenytoin sodium extemporaneous suspension. The physical, chemical and microbiological stability of phenytoin sodium suspension is analyzed at various temperatures.
- Published
- 2021
6. Antimicrobial efficacy of extracts of Saudi Arabian desert Terfezia claveryi truffles
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Hani M.J. Khojah, Osama B. Abdelhalim, Mahmoud A.H. Mostafa, and EL-Sayed E. Habib
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General Agricultural and Biological Sciences - Published
- 2022
7. Dual effect biodegradable ciprofloxacin loaded implantable matrices for osteomyelitis: controlled release and osteointegration
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Samar El Achy, Ahmed F. Hanafy, Hany S.M. Ali, and El-Sayed E. Habib
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Materials science ,Polymers ,Scanning electron microscope ,Polyesters ,Pharmaceutical Science ,02 engineering and technology ,Molding (process) ,engineering.material ,010402 general chemistry ,01 natural sciences ,Osseointegration ,Differential scanning calorimetry ,Coating ,Ciprofloxacin ,Drug Discovery ,Animals ,Porosity ,Pharmacology ,chemistry.chemical_classification ,Calorimetry, Differential Scanning ,Organic Chemistry ,Osteomyelitis ,Polymer ,021001 nanoscience & nanotechnology ,Controlled release ,Anti-Bacterial Agents ,Rats ,0104 chemical sciences ,Drug Liberation ,chemistry ,Delayed-Action Preparations ,engineering ,0210 nano-technology ,Biomedical engineering - Abstract
Ciprofloxacin biodegradable implantable matrices (CPX-IMs) of tailored porous surfaces were fabricated by hot melt injection molding of poly-l-lactic acid (PLLA) followed by coating with PLLA/sodium chloride. CPX-IDs were designed to have a non-porous coat (NPC) or a porous coat of small pore size (SPC; 150-250 µm) or a large pore size (LPC; 250-350 µm). CPX-IMs surface pore size was confirmed by scanning electron microscope. The hardness of NPC, LPC, and SPC CPX-IMs were 58 ± 2.8, 53 ± 1.9, and 50 ± 2.1 N, respectively. The measured porosity values were 41.2 ± 1.53, 65.2 ± 1.1, and 60.7 ± 1.2%, respectively. Differential scanning calorimetry was employed to study the compatibility of ingredients, the effect of injection molding on polymer properties, and implants degradation. Coating of CPX-IMs prolonged drug release to reach a value of 90% release in 40 days. Antibacterial activity tests showed sufficiency of CPX to inhibit pathogens known to cause osteomyelitis. The in vivo study showed tissue compatibilities of the inserted matrices in tested rats with no sign of infection throughout the experiment period. SPC and LPC CPX-IMs demonstrated a better osteointegration, cell adhesion, and infiltration of different types of bone cells within implants structure compared to the non-porous matrix. Furthermore, LPC CPX-IMs showed a superior bone cell attachment and osteointegration relative to SPC CPX-IMs. Findings of this study confirmed the impact of porosity and pore sizes on cell proliferation and fracture healing concurrently with the sustained local antibiotic therapy for treatment or prevention of osteomyelitis.
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- 2018
8. Synthesis, biological evaluation and molecular modeling study of some new methoxylated 2-benzylthio-quinazoline-4( 3H )-ones as nonclassical antifolates
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Hussein I. El-Subbagh, El-Sayed E. Habib, Mahmoud N. Nagi, Shahenda M. El-Messery, Ghada S. Hassan, and Sarah T. Al-Rashood
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Models, Molecular ,0301 basic medicine ,Molecular model ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Microbial Sensitivity Tests ,01 natural sciences ,Biochemistry ,Inhibitory Concentration 50 ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Discovery ,Quinazoline ,medicine ,Molecular Biology ,IC50 ,Biological evaluation ,chemistry.chemical_classification ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Antimicrobial ,In vitro ,Anti-Bacterial Agents ,0104 chemical sciences ,Amino acid ,Ciprofloxacin ,030104 developmental biology ,Quinazolines ,Folic Acid Antagonists ,Molecular Medicine ,Drug Screening Assays, Antitumor ,medicine.drug - Abstract
A new series of 2,3,6-substituted-quinazolin-4-ones was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 28 and 61 proved to be active DHFR inhibitors with IC50 0.02 and 0.01 μM, respectively. Molecular modeling studies concluded that recognition with the key amino acid Phe34 is essential for binding and hence DHFR inhibition. Compounds 34, 56 and 66 showed broad spectrum antimicrobial activity comparable to Gentamicin and Ciprofloxacin. Compounds 40 and 64 showed broad spectrum antitumor activity toward several tumor cell lines and proved to be 10 fold more active than 5-FU, with GI50 MG-MID values of 2.2 and 2.4 μM, respectively.
- Published
- 2016
9. The rational design, synthesis, and antimicrobial investigation of 2-Amino-4-Methylthiazole analogues inhibitors of GlcN-6-P synthase
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Abdelsattar M. Omar, El-Sayed E. Habib, Hamada S. Abulkhair, Saleh Ihmaid, Hany E.A. Ahmed, Sahar Ahmed, and Sultan S. Althagfan
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Staphylococcus aureus ,Antifungal Agents ,Lysis ,Molecular model ,Aspergillus oryzae ,Microbial Sensitivity Tests ,01 natural sciences ,Biochemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Glucosamine ,Pseudomonas ,Candida albicans ,Drug Discovery ,Escherichia coli ,Enzyme Inhibitors ,Binding site ,Molecular Biology ,Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) ,Dose-Response Relationship, Drug ,Molecular Structure ,ATP synthase ,biology ,010405 organic chemistry ,Organic Chemistry ,Rational design ,Antimicrobial ,In vitro ,Anti-Bacterial Agents ,0104 chemical sciences ,Micrococcus luteus ,Thiazoles ,010404 medicinal & biomolecular chemistry ,chemistry ,Drug Design ,biology.protein ,Aspergillus niger ,Bacillus subtilis - Abstract
A series of novel 2-Amino-4-Methylthiazole analogs were developed via three-step reaction encompassing hydrazine-1-carboximidamide motif to combat Gram-positive and Gram-negative bacterial and fungal infections. Noticeably, the thiazole-carboximidamide derivatives 4a-d displayed excellent antimicrobial activity and the most efficacious analogue 4d with MIC/MBC values of 0.5 and 4 μg/mL, compared to reference drugs with very low toxicity to mammalian cells, resulting in a prominent selectivity more than 100 folds. Microscopic investigation of 4d biphenyl analogue showed cell wall lysis and promote rapid bactericidal activity though disrupting the bacterial membrane. In addition, an interesting in vitro investigation against GlcN-6-P Synthase Inhibition was done which showed potency in the nanomolar range. Meanwhile, this is the first study deploying a biomimicking strategy to design potent thiazole-carboximidamides that targeting GlcN-6-P Synthase as antimicrobial agents. Importantly, Molecular modeling simulation was done for the most active 4d analogue to study the interaction of this analogue which showed good binding propensity to glucosamine binding site which support the in vitro data.
- Published
- 2020
10. Antibacterial, antibiofilm and molecular modeling study of some antitumor thiazole based chalcones as a new class of DHFR inhibitors
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Shahenda M. El-Messery, Abdulmalik Alqurshi, Waad D. Alrohily, El-Sayed E. Habib, Hussein I. El-Subbagh, and Mahmoud E. Habib
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0301 basic medicine ,Molecular model ,Gram-positive bacteria ,030106 microbiology ,Microbial Sensitivity Tests ,Gram-Positive Bacteria ,Microbiology ,03 medical and health sciences ,Pyrimidine analogue ,chemistry.chemical_compound ,Chalcones ,Gram-Negative Bacteria ,Quinazoline ,Thiazole ,chemistry.chemical_classification ,biology ,Chemistry ,biology.organism_classification ,Antimicrobial ,Combinatorial chemistry ,Anti-Bacterial Agents ,Molecular Docking Simulation ,Tetrahydrofolate Dehydrogenase ,030104 developmental biology ,Infectious Diseases ,Enzyme ,Biofilms ,Folic Acid Antagonists ,Bacteria ,Protein Binding - Abstract
Some synthesized antitumor derivatives of thiazole based chalcones including thiazolo[2,3-b]quinazoline and pyrido[4,3-d]thiazolo[3,2-a]pyrimidine analogues were subjected to be tested against standard microbial strains. Compound 18 showed higher activity against both Gram-positive and Gram-negative bacteria with MIC of 1.0, 1.0, 2.0, 2.0 and 4.0 μg/ml against S. aureus, B. subtilis, M. luteus, E. coli and P. aeuroginosa respectively which is better than ampicillin and very relative to ciprofloxacin standards. Moreover, this compound shows a good anti-biofilm activity against the Gram positive bacteria. Molecular docking studies of synthesized compounds against DHFR enzyme were carried out. Interestingly, active anticancer candidates 22,38, 40 and 41 in addition to most active antimicrobial agents 15, 18 and 20 bind to DHFR with nearly the same amino acid residues as MTX especially mentioning Arg28, Arg70, Asn64 and Lys68 which support our hypothesis that these compounds could act as antitumor or antibacterial via DHFR inhibition. Flexible alignment and surface mapping techniques have further provided lipophilic distributions supporting effective binding to DHFR. ADMET calculations for compounds 15, 18 and 20 suggested that they could be good orally absorbed antibacterial agents while compound 38 could be an orally absorbed anticancer agent with diminished toxicity. The results highlight studied thiazole based chalcones as efficient leads for designing new future antibacterial drug candidates.
- Published
- 2019
11. Targeting microbial resistance: Synthesis, antibacterial evaluation, DNA binding and modeling study of new chalcone-based dithiocarbamate derivatives
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Hamad M. Alkahtani, Ghada S. Hassan, Shahenda M. El-Messery, Sara T. Al-Rashood, Marwa Ayman, Abdulrahman A. Almehizia, and El-Sayed E. Habib
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Chalcone ,Gram-negative bacteria ,Microbial Sensitivity Tests ,Neisseria meningitidis ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Structure-Activity Relationship ,Chalcones ,Thiocarbamates ,Catalytic Domain ,Drug Discovery ,Dithiocarbamate ,Molecular Biology ,chemistry.chemical_classification ,biology ,Molecular Structure ,010405 organic chemistry ,Colistin ,Organic Chemistry ,Active site ,DNA ,biology.organism_classification ,Ethanolaminephosphotransferase ,Combinatorial chemistry ,Intercalating Agents ,0104 chemical sciences ,Anti-Bacterial Agents ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,Klebsiella pneumoniae ,Enzyme ,chemistry ,Docking (molecular) ,Doxorubicin ,Pseudomonas aeruginosa ,biology.protein ,Macromolecule - Abstract
New dithiocarbamate chalcone-based derivatives were synthesized, their structures were elucidated using different spectroscopic techniques. They were subjected to antimicrobial screening against selected Gram negative bacteria focusing on microbial resistance. Bacterial resistance was targeted via phosphoethanolamine transferase enzyme. Most of the synthesized compounds showed equal or higher activity to colistin standard. Compound 24 proved to be the most active candidate with MIC of 8 µg/ml against both Ps12 and K4 and MBC of 32 µg/ml against Ps12 and 16 µg/ml against K4 Molecular docking study showed that 20, 22, 24 and 25 had good binding affinity with active site residues via Thr280. DNA macromolecule was further targeted. Compounds 28 and 34 were recorded to have better DNA binding than doxurubucin with IC50 of 27.48 and 30.97 µg/ml respectively, suggesting that it could have a role in their higher antibacterial effect. Their docking into DNA has shown a clear intercalation matching with antibacterial data. Pharmacokinetics parameters of active compounds showed that they have better absorption through GIT.
- Published
- 2018
12. Synthesis, Biological Evaluation, and Molecular Docking of Novel Thiazoles and [1,3,4]Thiadiazoles Incorporating Sulfonamide Group as DHFR Inhibitors
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Shojaa Abed El-Motairi, Hany E.A. Ahmed, El-Sayed E. Habib, Khaled D. Khalil, and Sayed M. Riyadh
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0301 basic medicine ,Bioengineering ,Microbial Sensitivity Tests ,01 natural sciences ,Biochemistry ,03 medical and health sciences ,Structure-Activity Relationship ,Thiadiazoles ,Cell Line, Tumor ,Humans ,Molecular Biology ,Biological evaluation ,chemistry.chemical_classification ,Sulfonamides ,Bacteria ,010405 organic chemistry ,Spectrum Analysis ,Fungi ,General Chemistry ,General Medicine ,Combinatorial chemistry ,0104 chemical sciences ,Sulfonamide ,Molecular Docking Simulation ,Thiazoles ,030104 developmental biology ,chemistry ,DNA Gyrase ,Biofilms ,Molecular Medicine ,Folic Acid Antagonists ,Drug Screening Assays, Antitumor ,Anti biofilm - Abstract
2-(1-{4-[(4-Methylphenyl)sulfonamido]phenyl}ethylidene)thiosemicarbazide (3) was exploited as a starting material for the synthesis of two novel series of 5-arylazo-2-hydrazonothiazoles 6a - 6j and 2-hydrazono[1,3,4]thiadiazoles 10a - 10d, incorporating sulfonamide group, through its reactions with appropriate hydrazonoyl halides. The structures of the newly synthesized products were confirmed by spectral and elemental analyses. Also, the antimicrobial, anticancer, and DHFR inhibition potency for two series of thiazoles and [1,3,4]thiadiazoles were evaluated and explained by molecular docking studies and SAR analysis.
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- 2018
13. Biotechnological applications of quorum sensing inhibition as novel therapeutic strategies for multidrug resistant pathogens
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Abdelaziz Elgaml, El-Sayed E. Habib, and Mona I. Shaaban
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0301 basic medicine ,030106 microbiology ,Virulence ,medicine.disease_cause ,Microbiology ,03 medical and health sciences ,Drug Resistance, Multiple, Bacterial ,Gram-Negative Bacteria ,medicine ,Animals ,Humans ,biology ,Pseudomonas aeruginosa ,Biofilm ,Quorum Sensing ,Pathogenic bacteria ,biology.organism_classification ,Adaptation, Physiological ,Acinetobacter baumannii ,Anti-Bacterial Agents ,Quorum sensing ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,Autoinducer ,Gram-Negative Bacterial Infections ,Bacteria - Abstract
High incidence of antibiotic resistance among bacterial clinical isolates necessitates the discovery of new targets for inhibition of microbial pathogenicity, without stimulation of microbial resistance. This could be achieved by targeting virulence determinants, which cause host damage and disease. Many pathogenic bacteria elaborate signaling molecules for cellular communication. This signaling system is named quorum sensing system (QS), and it is contingent on the bacterial population density and mediated by signal molecules called pheromones or autoinducers (AIs). Bacteria utilize QS to regulate activities and behaviors including competence, conjugation, symbiosis, virulence, motility, sporulation, antibiotic production, and biofilm formation. Hence, targeting bacterial communicating signals and suppression of QS exhibit a fundamental approach for competing microbial communication. In this review, we illustrate the common up to date approaches to utilize QS circuits in pathogenic bacteria, including Vibrio fischeri, Pseudomonas aeruginosa, Escherichia coli and Acinetobacter baumannii, as novel therapeutic targets.
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- 2018
14. Synthesis, antimicrobial, anti-biofilm evaluation, and molecular modelling study of new chalcone linked amines derivatives
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Shahenda M. El-Messery, Sarah T. Al-Rashood, Ghada S. Hassan, and El-Sayed E. Habib
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0301 basic medicine ,Models, Molecular ,Chalcone ,Antifungal Agents ,Microbial Sensitivity Tests ,Conjugated system ,Gram-Positive Bacteria ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Structure-Activity Relationship ,Amide ,Drug Discovery ,Amines ,Pharmacology ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Chemistry ,lcsh:RM1-950 ,Fungi ,General Medicine ,Chalcones linked amines ,Carbon-13 NMR ,Antimicrobial ,Combinatorial chemistry ,0104 chemical sciences ,molecular modelling ,Anti-Bacterial Agents ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,antimicrobial/anti-biofilm activity ,Biofilms ,Proton NMR ,c-di-GMP inhibition ,Hydrophobic and Hydrophilic Interactions ,Anti biofilm ,Research Paper - Abstract
A series of amide chalcones conjugated with different secondary amines were synthesised and characterised by different spectroscopic techniques 1H NMR, 13C NMR, and ESI-MS. They were screened for in vitro antibacterial activity. Compounds 36, 37, 38, 42, and 44 are the most active among the synthesised series exhibiting MIC value of 2.0–10.0 µg/ml against different bacterial strains. Compound 36 was equipotent to the standard drug Ampicillin displaying MBC value of 2.0 µg/ml against the bacterial strain Staphylococcus aureus. The products were screened for anti-biofilm activity. Compounds 36, 37, and 38 exhibited promising anti-biofilm activity with IC50 value ranges from 2.4 to 8.6 µg. Molecular modelling was performed suggesting parameters of signalling anti-biofilm mechanism. AspB327 HisB340 (arene–arene interaction) and IleB328 amino acid residues seemed of higher importance to inhibit c-di-GMP. Hydrophobicity may be crucial for activity. ADME calculations suggested that compounds 36, 37, and 38 could be used as good orally absorbed anti-biofilm agents.
- Published
- 2018
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15. Synthesis, biological evaluation and molecular modeling study of 2-(1,3,4-thiadiazolyl-thio and 4-methyl-thiazolyl-thio)-quinazolin-4-ones as a new class of DHFR inhibitors
- Author
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Hussein I. El-Subbagh, Ghada S. Hassan, Sarah T. Al-Rashood, Fatmah A.M. Al-Omary, Shahenda M. El-Messery, El-Sayed E. Habib, and Mahmoud N. Nagi
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Models, Molecular ,Staphylococcus aureus ,Antifungal Agents ,Molecular model ,Stereochemistry ,medicine.drug_class ,Clinical Biochemistry ,Antibiotics ,Pharmaceutical Science ,Thio ,Antineoplastic Agents ,Biochemistry ,Structure-Activity Relationship ,Cell Line, Tumor ,Candida albicans ,Drug Discovery ,Escherichia coli ,medicine ,Humans ,Molecular Biology ,Cell Proliferation ,Quinazolinones ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Molecular Structure ,Organic Chemistry ,Antimicrobial ,In vitro ,Anti-Bacterial Agents ,Amino acid ,Tetrahydrofolate Dehydrogenase ,chemistry ,Toxicity ,Folic Acid Antagonists ,Molecular Medicine ,Gentamicin ,Drug Screening Assays, Antitumor ,Bacillus subtilis ,medicine.drug - Abstract
A new series of 2-(1,3,4-thiadiazolyl- or 4-methyl-thiazolyl)thio-6-substituted-quinazolin-4-one analogs was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 29, 34, and 39 proved to be the most active DHFR inhibitors with IC50 values range of 0.1-0.6 μM. Compounds 28, 31 and 33 showed remarkable broad-spectrum antimicrobial activity comparable to the known antibiotic Gentamicin. Compounds 26, 33, 39, 43, 44, 50, 55 and 63 showed broad spectrum antitumor activity with GI values range of 10.1-100%. Molecular modeling study concluded that recognition with key amino acid Glu30, Phe31 and Phe34 is essential for binding. ADMET properties prediction of the active compounds suggested that compounds 29 and 34 could be orally absorbed with diminished toxicity.
- Published
- 2014
16. Pyrimidine-5-carbonitriles – part III: synthesis and antimicrobial activity of novel 6-(2-substituted propyl)-2,4-disubstituted pyrimidine-5-carbonitriles
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Omar A. Al-Deeb, Ali A. El-Emam, El-Sayed E. Habib, Abdulghafoor A. Al-Turkistani, Ebtehal S. Al-Abdullah, and Nasser R. El-Brollosy
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biology ,Pyrimidine ,Aryl ,Organic Chemistry ,Dimethylaniline ,Ether ,Antimicrobial ,biology.organism_classification ,Medicinal chemistry ,chemistry.chemical_compound ,chemistry ,Acetone ,Organic chemistry ,Candida albicans ,Antibacterial activity - Abstract
The reaction of 6-(2-methylpropyl or 2-phenylpropyl)-2-thiouracil-5-carbonitriles (4a,b) with various arylmethyl halides, 2-bromoethyl methyl ether, benzyl chloromethyl ether, and 2-bromomethyl-5-nitrofuran in N,N-dimethylformamide or acetone yielded the corresponding substituted thio-3,4-dihydro-4-oxopyrimidine-5-carbonitrile analogues 5a–h, 6a,b, 7, and 8a,b, respectively. Treatment of 5c with phosphorus oxychloride and N,N-dimethylaniline yielded the 4-chloropyrimidine derivative 9, which was allowed to react with various arylthiols, arylamines, and 1-substituted piperazines to yield the respective 4-arylthio 10a–d, 4-arylamino 11a–d, and 4-piperazino 12a,b derivatives. The newly synthesized compounds were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 5e, 5f, 5g,h, 7, 8a,b, and 12a display marked antibacterial activity, particularly against the Gram-positive bacteria. None of these compounds are active against C. albicans.
- Published
- 2013
17. Pyrimidine-5-carbonitriles II: Synthesis and Antimicrobial Activity of Novel 6-Alkyl-2,4-disubstituted pyrimidine-5-carbonitriles
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Ebtehal S. Al-Abdullah, Ali A. El-Emam, Omar A. Al-Deeb, El-Sayed E. Habib, Nasser R. El-Brollosy, and Abdulghafoor A. Al-Turkistani
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Models, Molecular ,Antifungal Agents ,Magnetic Resonance Spectroscopy ,Pyrimidine ,Stereochemistry ,Microbial Sensitivity Tests ,chemistry.chemical_compound ,Anti-Infective Agents ,X-Ray Diffraction ,Candida albicans ,Nitriles ,Drug Discovery ,Alkyl ,chemistry.chemical_classification ,Bacteria ,biology ,General Medicine ,Pathogenic fungus ,Antimicrobial ,biology.organism_classification ,In vitro ,Anti-Bacterial Agents ,Molecular Weight ,Pyrimidines ,Solubility ,chemistry ,Indicators and Reagents ,Antibacterial activity - Abstract
New series of 6-alkyl-2,4-disubstituted pyrimidine-5-carbonitriles namely, 6-alkyl-2-thiouracil-5-carbonitriles 4c,d, 6-alkyl-2-arylmethylsulfanyl-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 5a-p, 6-alkyl-2-(2-methoxyethylsulfanyl)-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 6a-d, 6-alkyl-2-benzyloxymethylsulfanyl-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 7a-c, 6-alkyl-2-(5-nitrofuran-2-ylmethylsulfanyl)-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 8a-d, 6-alkyl-4-arylthio-2-(benzylsulfanyl)pyrimidine-5-carbonitriles 10a, b and 2-benzylsulfanyl-4-[4-(2-methoxyphenyl)-1-piperazinyl]-6-pentylpyrimidine-5-carbonitrile 11, were synthesized and tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 4d, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5 l, 5p, 7a, 7b, 7c, 8a, 8b, 8c, 8d and 11 -displayed marked antibacterial activity particularly against the tested Gram-positive bacteria. Meanwhile, none of these compounds were proved to be active against Candida albicans.
- Published
- 2013
18. Comparative Studies on Staphylococcus Aureus Isolates Associated with Infections in Diabetic and Non-Diabetic Patients
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Wael El-Naggar, El-Sayed E. Habib, and Ramadan Hassan
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Staphylococcus aureus ,business.industry ,medicine ,medicine.disease_cause ,business ,Non diabetic ,Microbiology - Published
- 2012
19. Synthesis, antimicrobial and anti-inflammatory activities of novel 5-(1-adamantyl)-1,3,4-thiadiazole derivatives
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Adnan A. Kadi, El-Sayed E. Habib, Ihsan A. Shehata, Tarek M. Ibrahim, Ali A. El-Emam, and Ebtehal S. Al-Abdullah
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Magnetic Resonance Spectroscopy ,Gram-negative bacteria ,Stereochemistry ,Carboxylic acid ,Anti-Inflammatory Agents ,Microbial Sensitivity Tests ,Chemical synthesis ,Mass Spectrometry ,Acetic acid ,chemistry.chemical_compound ,Anti-Infective Agents ,Candida albicans ,Thiadiazoles ,Drug Discovery ,Antibacterial agent ,Pharmacology ,chemistry.chemical_classification ,Bacteria ,biology ,Organic Chemistry ,General Medicine ,Antimicrobial ,biology.organism_classification ,chemistry - Abstract
New 1-adamanyl-1,3,4-thiadiazole derivatives namely, 5-(1-adamantyl)-1,3,4-thiadiazoline-2-thione 3 , 5-(1-adamantyl)-3-(benzyl- or 4-substituted benzyl)-1,3,4-thiadiazoline-2-thione 4a–d , 5-(1-adamantyl)-3-(4-substituted-1-piperazinylmethyl)-1,3,4-thiadiazoline-2-thiones 5a–c , 2-[5-(1-adamantyl)-2-thioxo-1,3,4-thiadiazolin-3-yl]acetic acid 7 , (±)-2-[5-(1-adamantyl)-2-thioxo-1,3,4-thiadiazolin-3-yl]propionic acid 9 , 3-[5-(1-adamantyl)-2-thioxo-1,3,4-thiadiazolin-3-yl]propionic acid 11 , N -[5-(1-adamantyl)-1,3,4-thiadiazol-2-yl]- N ′-arylthioureas 15a–c and 5-(1-adamantyl)-1,3,4-thiadiazoline-2-one 16 , were synthesized and tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans . Compounds 7 , 9 , 15b and 15c displayed marked activity against the tested Gram-positive bacteria, while compound 3 was highly active against the tested Gram-negative bacteria. Compounds 4b , 7 and 15c were weakly or moderately active against C. albicans . In addition, the in vivo anti-inflammatory activity of the synthesized compounds was determined using the carrageenan-induced paw oedema method in rats. The propionic acid derivative 9 produced good dose-dependent anti-inflammatory activity.
- Published
- 2010
20. Non-classical antifolates. Part 2: Synthesis, biological evaluation, and molecular modeling study of some new 2,6-substituted-quinazolin-4-ones
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Hussein I. El-Subbagh, Sami G. Abdel-Hamide, Laila A. Abou-Zeid, Mahmoud N. Nagi, Alaa A.-M. Abdel-Aziz, Abdulrahman M. Al-Obaid, Mohamed A. Al-Omar, El-Sayed E. Habib, Adel S. El-Azab, and Fatmah A.M. Al-Omary
- Subjects
Molecular model ,Stereochemistry ,Static Electricity ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Molecular Dynamics Simulation ,Biochemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Anti-Infective Agents ,Cell Line, Tumor ,Drug Discovery ,Quinazoline ,Humans ,Structure–activity relationship ,Molecular Biology ,Quinazolinones ,Biological evaluation ,Chemistry ,Organic Chemistry ,Biological activity ,Antimicrobial ,Combinatorial chemistry ,In vitro ,Tetrahydrofolate Dehydrogenase ,Folic Acid Antagonists ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Pharmacophore ,Hydrophobic and Hydrophilic Interactions - Abstract
A new series of 2,6-substituted-quinazolin-4-ones was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 22, 33-37, 39-43, and 45 proved to be active DHFR inhibitors with IC(50) range of 0.4-1.0microM. Compound 18 showed broad-spectrum antimicrobial activity comparable to the known antibiotic gentamicin. Compounds 34 and 36 showed antitumor activity at GI(50) (MG-MID) concentrations of 11.2, and 24.2microM, respectively. Molecular modeling study including flexible alignment; electrostatic, hydrophobic mappings; and pharmacophore prediction were performed. A main featured pharmacophore model was developed which justifies the importance of the main pharmacophoric groups as well as of their relative distances. The substitution pattern and spatial considerations of the pi-systems in regard to the quinazoline nucleus proved critical for biological activity.
- Published
- 2010
21. Biosynthesis of Fattiviracin FV-8, an Antiviral Agent
- Author
-
Masaru Uyeda, Kazumi Yokomizo, Keitarou Suzuki, and El-Sayed E. Habib
- Subjects
Antifungal Agents ,Stereochemistry ,Carbohydrates ,Biology ,Antiviral Agents ,Applied Microbiology and Biotechnology ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Acetic acid ,Biosynthesis ,Molecular Biology ,chemistry.chemical_classification ,Cell-Free System ,Strain (chemistry) ,Streptomycetaceae ,Organic Chemistry ,Fatty acid ,General Medicine ,Carbohydrate ,biology.organism_classification ,Cerulenin ,Streptomyces ,Culture Media ,Glucose ,chemistry ,Streptomyces microflavus ,Carbohydrate Metabolism ,Glycolipids ,Biotechnology - Abstract
Streptomyces microflavus strain No. 2445 produces many derivatives of fattiviracin antibiotics. The major product of these derivatives is fattiviracin FV-8, which consists of four glucose and two trihydroxy fatty acid residues. We found that this strain has the ability to convert several sugars in the culture medium to glucose, and the glucose added to the medium is directly incorporated into the FV-8 molecule. Two trihydroxy fatty acid residues in the FV-8 molecule are derived from acetic acid, and production of FV-8 is inhibited by the addition of cerulenin, which is an inhibitor of fatty acid biosynthesis.
- Published
- 2001
22. Nonclassical antifolates, part 4. 5-(2-aminothiazol-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiols as a new class of DHFR inhibitors: synthesis, biological evaluation and molecular modeling study
- Author
-
Sarah T. Al-Rashood, Hussein I. El-Subbagh, Bassem S. El-Menshawi, Yasmin S. Abulfadl, Walid Fayad, Salwa M. El-Hallouty, Shahenda M. El-Messery, Marwa I. Shabayek, Khaled M. Mohamed, Ghada S. Hassan, El-Sayed E. Habib, and Fatmah A.M. Al-Omary
- Subjects
Male ,Models, Molecular ,Molecular model ,Stereochemistry ,Protein Conformation ,Antineoplastic Agents ,Chemistry Techniques, Synthetic ,chemistry.chemical_compound ,Structure-Activity Relationship ,Cell Line, Tumor ,parasitic diseases ,Drug Discovery ,medicine ,Animals ,Doxorubicin ,DHFR Inhibitor ,IC50 ,Biological evaluation ,Pharmacology ,chemistry.chemical_classification ,Antiparasitic Agents ,Organic Chemistry ,1,2,4-Triazole ,General Medicine ,Schistosoma mansoni ,Triazoles ,Antimicrobial ,Amino acid ,Tetrahydrofolate Dehydrogenase ,Methotrexate ,chemistry ,Folic Acid Antagonists ,Female ,Drug Screening Assays, Antitumor ,medicine.drug - Abstract
A new series of compounds possessing 5-(2-aminothiazol-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol skeleton was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, antitumor and schistosomicidal activities. Four active compounds were allocated, the antibacterial 22 (comparable to gentamicin and ciprofloxacin), the schistosomicidal 29 (comparable to praziquantel), the DHFR inhibitor 34 (IC50 0.03 μM, 2.7 fold more active than MTX), and the antitumor 36 (comparable to doxorubicin). Molecular modeling studies concluded that recognition with key amino acid Leu4 and Val1 is essential for DHFR binding. Flexible alignment and surface mapping revealed that the obtained model could be useful for the development of new class of DHFR inhibitors.
- Published
- 2013
23. Synthesis and antimicrobial activity of novel 5-(1-adamantyl)-2-aminomethyl-4-substituted-1,2,4-triazoline-3-thiones
- Author
-
Mohamed A. Al-Omar, El-Sayed E. Habib, Khalid A. Al-Rashood, Ali A. El-Emam, and Abdul-Malek S. Al-Tamimi
- Subjects
Stereochemistry ,Adamantane ,Microbial Sensitivity Tests ,Mannich Bases ,chemistry.chemical_compound ,Anti-Infective Agents ,Drug Discovery ,Candida albicans ,Organic chemistry ,Pharmacology ,FORMALDEHYDE SOLUTION ,biology ,Bacteria ,Organic Chemistry ,Thiones ,General Medicine ,Pathogenic fungus ,Triazoles ,Antimicrobial ,biology.organism_classification ,Corpus albicans ,chemistry ,Antibacterial activity - Abstract
The reaction of 5-(1-adamantyl)-4-substituted-1,2,4-triazoline-3-thione 5a,b and 10a,b with formaldehyde solution and various primary aromatic amines or 1-substituted piperazines yielded the corresponding N-Mannich bases 6a-o, 7a-g and 11a-i. The newly synthesized N-Mannich bases 6a-o, 7a-g and 11a-i were tested for in vitro inhibitory activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. The compounds 6j, 6l, 6m, 7a, 7b, 7c, 7d, 7f, 11a, 11b, 11c, 11d, 11e, 11f, 11h and 11i displayed moderate to good activity against the tested Gram-positive bacteria, while compounds 7c, 11c, 11d, 11f and 11h showed potent broad spectrum antibacterial activity. None of the newly synthesized compounds were proved to possess marked activity against C. albicans.
- Published
- 2012
24. Nonclassical antifolates, part 3: synthesis, biological evaluation and molecular modeling study of some new 2-heteroarylthio-quinazolin-4-ones
- Author
-
Shahenda M. El-Messery, Hussein I. El-Subbagh, Fatmah A.M. Al-Omary, Ghada S. Hassan, Mahmoud N. Nagi, and El-Sayed E. Habib
- Subjects
Models, Molecular ,Molecular model ,Stereochemistry ,Antineoplastic Agents ,HL-60 Cells ,Microbial Sensitivity Tests ,Molecular Dynamics Simulation ,Gram-Positive Bacteria ,Structure-Activity Relationship ,Protein structure ,Anti-Infective Agents ,Cell Line, Tumor ,parasitic diseases ,Drug Discovery ,Gram-Negative Bacteria ,Structure–activity relationship ,Molecule ,Humans ,IC50 ,Cell Proliferation ,Quinazolinones ,Pharmacology ,chemistry.chemical_classification ,Molecular Structure ,Organic Chemistry ,General Medicine ,Antimicrobial ,Combinatorial chemistry ,Amino acid ,Protein Structure, Tertiary ,Tetrahydrofolate Dehydrogenase ,chemistry ,Models, Chemical ,Cell culture ,Biocatalysis ,MCF-7 Cells ,Quinazolines ,Folic Acid Antagonists - Abstract
A new series of 2-heteroarylthio-6-substituted-quinazolin-4-one analogs was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 21, 25, and 39 proved to be active DHFR inhibitors with IC50 range of 0.3–0.8 μM. Compounds 25, 28, 33, 35 and 36 showed broad spectrum antimicrobial activity comparable to the known antibiotic gentamicin. Compound 29 showed broad spectrum antitumor activity toward several tumor cell lines with GI values range of 25.8–41.2%. Molecular modeling studies concluded that recognition with key amino acid Arg38 and Lys31 are essential for binding and biological activities. Flexible alignment; electrostatic and hydrophobic mappings revealed that the obtained model could be useful for the development of new DHFR inhibitors.
- Published
- 2012
25. Bacterial artificial chromosome clones of viruses comprising the towne cytomegalovirus vaccine
- Author
-
Andrew J. Davison, Michael A. McVoy, Larry Smith, El-Sayed E. Habib, Stuart P. Adler, and Xiaohong Cui
- Subjects
Viral Plaque Assay ,Chromosomes, Artificial, Bacterial ,Article Subject ,Health, Toxicology and Mutagenesis ,lcsh:Biotechnology ,lcsh:Medicine ,Cytomegalovirus ,Genome, Viral ,Biology ,Vaccines, Attenuated ,Genome ,Cell Line ,03 medical and health sciences ,Serial passage ,lcsh:TP248.13-248.65 ,Genotype ,Genetics ,medicine ,Humans ,Cloning, Molecular ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Bacterial artificial chromosome ,030306 microbiology ,Immunogenicity ,Viral Vaccine ,lcsh:R ,Viral Vaccines ,General Medicine ,Virology ,3. Good health ,Molecular Medicine ,Cytomegalovirus vaccine ,Biotechnology ,medicine.drug ,Research Article - Abstract
Bacterial artificial chromosome (BAC) clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts. Although its safety, immunogenicity, and efficacy have been evaluated in nearly a thousand human subjects, the vaccine itself has been little studied. Instead, genetic composition and in vitro growth properties have been inferred from studies of laboratory stocks that may not always accurately represent the viruses that comprise the vaccine. Here we describe the use of BAC cloning to define the genotypic and phenotypic properties of viruses from the Towne vaccine. Given the extensive safety history of the Towne vaccine, these BACs provide a logical starting point for the development of next-generation rationally engineered cytomegalovirus vaccines.
- Published
- 2011
26. Synthesis of novel 6-phenyl-2,4-disubstituted pyrimidine-5-carbonitriles as potential antimicrobial agents
- Author
-
Omar A. Al-Deeb, El-Sayed E. Habib, Ebtehal S. Al-Abdullah, Abdulrahman M. Al-Obaid, and Ali A. El-Emam
- Subjects
Spectrometry, Mass, Electrospray Ionization ,Gram-negative bacteria ,Magnetic Resonance Spectroscopy ,Pyrimidine ,Spectrophotometry, Infrared ,Stereochemistry ,Gram-positive bacteria ,Gram-Positive Bacteria ,Microbiology ,chemistry.chemical_compound ,Anti-Infective Agents ,Drug Discovery ,Candida albicans ,Gram-Negative Bacteria ,Nitriles ,Pharmacology ,biology ,Organic Chemistry ,General Medicine ,biology.organism_classification ,Antimicrobial ,Corpus albicans ,chemistry ,Antibacterial activity ,Bacteria - Abstract
New series of 6-phenyl-2,4-disubstituted pyrimidine-5-carbonitriles namely, 2-substitued thio-6-phenyl-3,4-dihydro-4-oxopyrimidine-5-carbonitriles (5a-d, 6, 7a-d, 8), 2-(4-chlorobenzylthio)-4-chloro-6-phenylpyrimidine-5-carbonitrile (9), 2-(4-chlorobenzylthio)-4-arylthio-6-phenylpyrimidine-5-carbonitriles (10a-d) and 2-(4-chlorobenzylthio)-4-arylamino-6-phenylpyrimidine-5-carbonitriles (11a-d) was synthesized and tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 5b, 5c, 6, 7a, 7b, 7c, 9 and 11a displayed marked antibacterial activity particularly against the tested Gram-positive bacteria, while compounds 6, 7c, 7d and 9 were moderately or weakly active against C. albicans.
- Published
- 2011
27. ChemInform Abstract: Fattiviracin A1, a Novel Antiherpetic Agent Produced by Streptomyces microflavus Strain No. 2445. Part 1. Taxonomy, Fermentation, Isolation, Physico-Chemical Properties and Structure Elucidation
- Author
-
Yoshiaki Miyamoto, Masaru Uyeda, El-Sayed E. Habib, and Kazumi Yokomizo
- Subjects
Fattiviracin-A1 ,Stereochemistry ,Chemistry ,Streptomyces microflavus ,Organic chemistry ,Fermentation ,General Medicine - Published
- 2010
28. ChemInform Abstract: Fattiviracin A1, a Novel Antiviral Agent Produced by Streptomyces microflavus Strain No. 2445. Part 2. Biological Properties
- Author
-
Keitarou Suzuki, Kazuhiko Nagao, Masaru Uyeda, Kazumi Yokomizo, El-Sayed E. Habib, Etsuko Kumagae, Yoshiaki Miyamoto, and Shinji Harada
- Subjects
Fattiviracin-A1 ,Biochemistry ,Strain (chemistry) ,Chemistry ,Biological property ,Streptomyces microflavus ,General Medicine - Published
- 2010
29. Involvement of transposon-like elements in penicillin gene cluster regulation
- Author
-
Mona I. Shaaban, Jonathan M. Palmer, Mohamed Mohamed Adel El-Sokkary, Nancy P. Keller, Wael El-Naggar, and El-Sayed E. Habib
- Subjects
Genetics ,Transposable element ,biology ,Mutant ,Penicillins ,biology.organism_classification ,Microbiology ,Molecular biology ,Aspergillus nidulans ,Article ,Penicillin ,Fungal Proteins ,chemistry.chemical_compound ,chemistry ,Gene Expression Regulation, Fungal ,Multigene Family ,Gene expression ,Gene cluster ,medicine ,DNA Transposable Elements ,Gene ,DNA ,medicine.drug - Abstract
Subtelomeric secondary metabolite (SM) gene clusters are frequently surrounded by DNA repeats and transposon-like elements. The Aspergillus nidulans penicillin cluster, 30 kb from the telomere of chromosome VI, is bordered by such elements. Deletions of penicillin telomere proximal and distal border regions resulted in decreased penicillin production. A 3.7 kb distal region called PbIa, consisting of the putative transposable element DNA-2, was examined further where its replacement by a pyrG marker presented a similar phenotype as loss of the global SM regulator LaeA, resulting in a decrease in penicillin gene expression and product formation. In contrast, placement of the pyrG marker on either side of PbIa had no effect on penicillin synthesis. A requirement for PbIa in penicillin production was also apparent in a histone deacetylase mutant, ΔhdaA, enhanced for penicillin production. Trans-complementation of the PbIa element near and within the terrequinone A cluster on chromosome V did not restore penicillin biosynthesis or increase production of terrequinone A. Taken together, this data provides evidence for transposon involvement in SM cluster regulation.
- Published
- 2009
30. Synthesis, Antimicrobial, and Antiinflammatory Activities of Novel 2-(1-Adamantyl)-5-substituted-1,3,4-oxadiazoles and 2-(1-Adamantylamino)-5-substituted-1,3,4-thiadiazoles
- Author
-
Nasser R. El-Brollosy, Adnan A. Kadi, El-Sayed E. Habib, Ali A. El-Emam, Tarek M. Ibrahim, and Omar A. Al-Deeb
- Subjects
Male ,Antifungal Agents ,Carboxylic acid ,Colony Count, Microbial ,Oxadiazole ,Adamantane ,Microbial Sensitivity Tests ,Gram-Positive Bacteria ,Chemical synthesis ,Rats, Sprague-Dawley ,Structure-Activity Relationship ,chemistry.chemical_compound ,Thiadiazoles ,Candida albicans ,Gram-Negative Bacteria ,Drug Discovery ,Pyridine ,Animals ,Organic chemistry ,Pharmacology ,chemistry.chemical_classification ,Oxadiazoles ,biology ,Chemistry ,Anti-Inflammatory Agents, Non-Steroidal ,Organic Chemistry ,Biological activity ,General Medicine ,biology.organism_classification ,Antimicrobial ,Combinatorial chemistry ,Anti-Bacterial Agents ,Rats - Abstract
Reaction of 1-adamantanecarbonyl chloride with certain carboxylic acid hydrazides in pyridine yielded the corresponding N-acyl adamantane-1-carbohydrazide derivatives 3a-j, which were cyclized to the corresponding 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles 4a-j via heating with phosphorus oxychloride. Treatment of 1-adamantylisothiocyanate with some carboxylic acid hydrazides in ethanol yielded the corresponding 1-acyl-4-(1-adamantyl)-3-thiosemicarbazides 7a-g, which were cyclized to the corresponding 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazole derivatives 8a-g. Compounds 4a-j, 7a-g, and 8a-g were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Several derivatives produced good or moderate activities particularly against the tested Gram-positive bacteria Bacillus subtilis. Meanwhile, compounds 4i and 8g displayed marked antifungal activity against C. albicans. In addition, the in vivo anti-inflammatory activity of the synthesized compounds was determined using the carrageenin-induced paw oedema method in rats. The oxadiazole derivatives 4c, 4g, 4i and 4j produced good dose-dependent anti-inflammatory activity.
- Published
- 2007
31. Production of hygromycin A analogs in Streptomyces hygroscopicus NRRL 2388 through identification and manipulation of the biosynthetic gene cluster
- Author
-
Sloan Ayers, Shuchi Gupta, Nadaraj Palaniappan, El-Sayed E. Habib, and Kevin A. Reynolds
- Subjects
DNA, Bacterial ,Peptidyl transferase ,Clinical Biochemistry ,Biochemistry ,chemistry.chemical_compound ,Open Reading Frames ,Biosynthesis ,Drug Discovery ,Gene cluster ,ORFS ,Cloning, Molecular ,Molecular Biology ,DNA Primers ,Pharmacology ,biology ,Base Sequence ,Gene Expression Profiling ,General Medicine ,Ribosomal RNA ,biology.organism_classification ,Streptomyces ,carbohydrates (lipids) ,Aminocyclitol ,genomic DNA ,CHEMBIO ,chemistry ,Cinnamates ,Multigene Family ,biology.protein ,Molecular Medicine ,Hygromycin B ,Streptomyces hygroscopicus - Abstract
Summary Hygromycin A, an antibiotic produced by Streptomyces hygroscopicus NRRL 2388, offers a distinct carbon skeleton structure for development of antibacterial agents targeting the bacterial ribosomal peptidyl transferase. A 31.5 kb genomic DNA region covering the hygromycin A biosynthetic gene cluster has been identified, cloned, and sequenced. The hygromycin gene cluster has 29 ORFs which can be assigned to hygromycin A resistance as well as regulation and biosynthesis of the three key moieties of hygromycin A (5-dehydro-α-L-fucofuranose, ( E )-3-(3,4-dihydroxyphenyl)-2-methylacrylic acid, and 2L-2-amino-2-deoxy-4,5- O -methylene- neo -inositol. The predicted Hyg26 protein has sequence homology to short-chain alcohol dehydrogenases and is assigned to the final step in production of the 5-dehydro-α-L-fucofuranose, catalyzing the reduction of α-L-fucofuranose. A hyg26 mutant strain was generated and shown to produce no hygromycin A but 5″-dihydrohygromycin A, 5″-dihydromethoxyhygromycin A, and a 5″-dihydrohygromycin A product lacking the aminocyclitol moiety. To the best of our knowledge, these shunt metabolites of biosynthetic pathway intermediates have not previously been identified. They provide insight into the ordering of the multiple unusual steps which compromise the convergent hygromycin A biosynthetic pathway.
- Published
- 2006
32. Biosynthetic origin of hygromycin A
- Author
-
El-Sayed E. Habib, Kevin A. Reynolds, and J. Neel Scarsdale
- Subjects
Peptidyl transferase ,Transamination ,Stereochemistry ,Decarboxylation ,Glycine ,Mannose ,chemistry.chemical_compound ,Chorismic acid ,Moiety ,Pharmacology (medical) ,Enzyme Inhibitors ,Pharmacology ,chemistry.chemical_classification ,biology ,Chemistry ,Biosynthesis ,biology.organism_classification ,Streptomyces ,Anti-Bacterial Agents ,Aminocyclitol ,Infectious Diseases ,chemistry ,Biochemistry ,Cinnamates ,Fermentation ,biology.protein ,Hygromycin B ,Streptomyces hygroscopicus - Abstract
Hygromycin A, an antibiotic produced by Streptomyces hygroscopicus , is an inhibitor of bacterial ribosomal peptidyl transferase. The antibiotic binds to the ribosome in a distinct but overlapping manner with other antibiotics and offers a different template for generation of new agents effective against multidrug-resistant pathogens. Reported herein are the results from a series of stable-isotope-incorporation studies demonstrating the biosynthetic origins of the three distinct structural moieties which comprise hygromycin A. Incorporation of [1- 13 C]mannose and intact incorporation of d -[1,2- 13 C 2 ]glucose into the 6-deoxy-5-keto- d -arabino-hexofuranose moiety are consistent with a pathway in which mannose is converted to an activated l -fucose, via a 4-keto-6-deoxy- d -mannose intermediate, with a subsequent unusual mutation of the pyranose to the corresponding furanose. The aminocyclitol moiety was labeled by d -[1,2- 13 C 2 ]glucose in a manner consistent with formation of myo -inositol and a subsequent unprecedented oxidation and transamination of the C-2 hydroxyl group to generate neo -inosamine-2. Incorporation of [ carboxy- 13 C]-4-hydroxybenzoic acid and intact incorporation of [2,3- 13 C 2 ]propionate are consistent with a polyketide synthase-type decarboxylation condensation to generate the 3,4-dihydroxy-α-methylcinnamic acid moiety of hygromycin A. No labeling of hygromycin A was observed when [3- 13 C]tyrosine, [3- 13 C]phenylalanine, or [ carboxy- 13 C]benzoic acid was used, suggesting that the 4-hydroxybenzoic acid is derived directly from chorismic acid. Consistent with this hypothesis was the observation that hygromycin A titers could be reduced by addition of N -(phosphonomethyl)-glycine (an inhibitor of chorismic acid biosynthesis) and restored by coaddition of 4-hydroxybenzoic acid. The convergent biosynthetic pathway established for hygromycin A offers significant versatility for applying the techniques of combinatorial and directed biosynthesis to production of new antibiotics which target the ribosomal peptidyl transferase activity.
- Published
- 2003
33. Synthesis, antimicrobial, and anti-inflammatory activity, of novel S-substituted and N-substituted 5-(1-adamantyl)-1,2,4-triazole-3-thiols
- Author
-
Tarek M. Ibrahim, Ebtehal S. Al-Abdullah, Ali A. El-Emam, Siham Lahsasni, Hanadi H. Asiri, and El-Sayed E. Habib
- Subjects
Male ,Stereochemistry ,Anti-Inflammatory Agents ,Formaldehyde ,Pharmaceutical Science ,1,2,4-triazoles ,Chloride ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Anti-Infective Agents ,Drug Discovery ,medicine ,Animals ,Sulfhydryl Compounds ,anti-inflammatory activity ,Candida albicans ,Original Research ,Pharmacology ,Drug Design, Development and Therapy ,antimicrobial activity ,Dose-Response Relationship, Drug ,biology ,Aryl ,1,2,4-Triazole ,Triazoles ,Antimicrobial ,biology.organism_classification ,Rats ,Ethyl bromoacetate ,chemistry ,adamantane derivatives ,N-Mannich bases ,Antibacterial activity ,medicine.drug - Abstract
Ebtehal S Al-Abdullah,1 Hanadi H Asiri,1 Siham Lahsasni,2 Elsayed E Habib,3 Tarek M Ibrahim,4 Ali A El-Emam1 1Department of Pharmaceutical Chemistry, College of Pharmacy, 2Department of Chemistry, College of Sciences, King Saud University, Riyadh, 3Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, Medinah, Saudi Arabia; 4Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt Abstract: The reaction of 5-(1-adamantyl)-4-phenyl-1,2,4-triazoline-3-thione (compound 5) with formaldehyde and 1-substituted piperazines yielded the corresponding N-Mannich bases 6a–f. The reaction of 5-(1-adamantyl)-4-methyl-1,2,4-triazoline-3-thione 8 with various 2-aminoethyl chloride yielded separable mixtures of the S-(2-aminoethyl) 9a–d and the N-(2-aminoethyl) 10a–d derivatives. The reaction of compound 5 with 1-bromo-2-methoxyethane, various aryl methyl halides, and ethyl bromoacetate solely yielded the S-substituted products 11, 12a–d, and 13. The new compounds were tested for activity against a panel of Gram-positive and Gram-negative bacteria and the pathogenic fungus Candida albicans. Compounds 6b, 6c, 6d, 6e, 6f, 10b, 10c, 10d, 12c, 12d, 12e, 13, and 14 displayed potent antibacterial activity. Meanwhile, compounds 13 and 14 produced good dose-dependent anti-inflammatory activity against carrageenan-induced paw edema in rats. Keywords: adamantane derivatives, 1,2,4-triazoles, N-Mannich bases, antimicrobial activity, anti-inflammatory activity
- Published
- 2014
34. Antiviral activity of fattiviracin FV-8 against human immunodeficiency virus type 1 (HIV-1)
- Author
-
Kazumi Yokomizo, Kazuhiko Nagao, El-Sayed E. Habib, Masaru Uyeda, and Shinji Harada
- Subjects
Herpesvirus 3, Human ,Anti-HIV Agents ,viruses ,Viral transformation ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Applied Microbiology and Biotechnology ,Biochemistry ,Antiviral Agents ,Virus ,Analytical Chemistry ,Microbiology ,Cell Line ,Dogs ,Viral entry ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Antibody-dependent enhancement ,Molecular Biology ,Vero Cells ,Dose-Response Relationship, Drug ,Host (biology) ,Viral culture ,Organic Chemistry ,virus diseases ,General Medicine ,Virology ,Streptomyces ,Influenza B virus ,Herpes simplex virus ,Glucose ,Influenza A virus ,Streptomyces microflavus ,Fatty Acids, Unsaturated ,HIV-1 ,Glycolipids ,Biotechnology - Abstract
A novel antiviral agent, fattiviracin FV-8, purified from the culture broth of Streptomyces microflavus strain No. 2445, showed potent antiviral activities against human immunodeficiency virus type 1 (HIV-1), herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and influenza A and B viruses. The action mechanism of fattiviracin FV-8 against HIV-1 was examined. As a result, the agent was thought to act on HIV-1 particles directly without lysis of the particles, and it affords the inhibition of viral entry into the host cells.
- Published
- 2001
35. Fattiviracin A1, a novel antiviral agent produced by Streptomyces microflavus strain No. 2445. II. Biological properties
- Author
-
Kazuhiko Nagao, Yoshiaki Miyamoto, Keitarou Suzuki, Etsuko Kumagae, Masaru Uyeda, Shinji Harada, El-Sayed E. Habib, and Kazumi Yokomizo
- Subjects
Herpesvirus 3, Human ,viruses ,Orthomyxoviridae ,Herpesvirus 1, Human ,Microbial Sensitivity Tests ,medicine.disease_cause ,Virus Replication ,Antiviral Agents ,Virus ,Microbiology ,Viral entry ,Drug Discovery ,Chlorocebus aethiops ,medicine ,Influenza A virus ,Animals ,Vero Cells ,Pharmacology ,biology ,Varicella zoster virus ,virus diseases ,biology.organism_classification ,Virology ,Streptomyces ,Herpes simplex virus ,Glucose ,Streptomyces microflavus ,Vero cell ,Fatty Acids, Unsaturated ,HIV-1 - Abstract
Fattiviracin A1, showed potent antiviral activities against herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), influenza A virus and human immunodeficiency virus type 1 (HIV-1). It showed no cytotoxicity against Vero cells. Fattiviracin A1 exhibited no significant antibacterial or antifungal activities. Treatment of HSV-1 with fattiviracin A1 decreased its infectivity to Vero cells. The mechanism of its antiviral activity may be due to inactivation of the viral particles and inhibition of viral entry into host cells.
- Published
- 1999
36. Fattiviracin A1, a novel antiherpetic agent produced by Streptomyces microflavus Strain No. 2445. I. Taxonomy, fermentation, isolation, physico-chemical properties and structure elucidation
- Author
-
El-Sayed E. Habib, Yoshiaki Miyamoto, Masaru Uyeda, and Kazumi Yokomizo
- Subjects
Pharmacology ,Chromatography ,Magnetic Resonance Spectroscopy ,biology ,Molecular Structure ,Chemistry ,Silica gel ,Streptomycetaceae ,Fast atom bombardment ,Spectrometry, Mass, Fast Atom Bombardment ,biology.organism_classification ,High-performance liquid chromatography ,Antiviral Agents ,Streptomyces ,chemistry.chemical_compound ,Drug Discovery ,Streptomyces microflavus ,Fermentation ,Side chain ,Simplexvirus ,Actinomycetales ,Chromatography, Thin Layer ,Chromatography, High Pressure Liquid - Abstract
A novel antiherpetic agent, fattiviracin A1, was isolated from the culture broth of strain No. 2445 identified as Streptomyces microflavus. It was purified through 1-butanol extraction, column chromatographies on Diaion HP-10 and silica gel and HPLC using a reverse phase column. The structure of fattiviracin A1 was determined by several spectroscopic experiments and chemical degradations. It is a new macrocyclic diester consisting of four D-glucose units and two (C24 and C33) hydroxy fatty acids. It is closely related to cycloviracins B1 and B2, but differs from these known compounds in both the length of its side chain and the sugar moiety.
- Published
- 1998
37. A Comparative study on gram-negative bacterial infections in Mansoura University Hospitals, Egypt
- Author
-
E. Abd-Elmagid, Wael El-Naggar, El-Sayed E. Habib, R. Ibrahim, and S. Gerorge
- Subjects
Microbiology (medical) ,Infectious Diseases ,Gram-negative bacterial infections ,business.industry ,Medicine ,General Medicine ,University hospital ,business ,Microbiology - Published
- 2010
38. P20 The effect of biofilm formation on the efficacy of different antimicrobials against bacterial clinical isolates
- Author
-
S. Kheira, R. El-Bagisy, Wael El-Naggar, P. Hassan, and El-Sayed E. Habib
- Subjects
Microbiology (medical) ,Infectious Diseases ,Chemistry ,Biofilm ,Pharmacology (medical) ,General Medicine ,Antimicrobial ,Microbiology - Published
- 2009
39. Structures of fattiviracin family, antiviral antibiotics
- Author
-
Kazumi Yokomizo, Keiko Murata, El-Sayed E. Habib, and Masaru Uyeda
- Subjects
Pharmacology ,chemistry.chemical_classification ,Molecular Structure ,medicine.drug_class ,Antibiotics ,Biological activity ,Biology ,Antiviral Agents ,In vitro ,Anti-Bacterial Agents ,chemistry ,Biochemistry ,Drug Discovery ,medicine ,Fatty Acids, Unsaturated ,Lactone
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