Ahmed H. Halawa

Synthesis, Reactions and Biological Evaluation of Some New Naphtho[2,1-b]furan Derivatives Bearing a Pyrazole Nucleus

Vilsmeier formylation of 2-(1-phenylhydrazonoethyl)naphtho[2,1-b]furan (2) gave 3-naphtho[2,1-b]furan-2-yl-1-phenyl-1H-pyrazole-4-carbaldehyde (3), which was reacted with C- and N-nucleophiles to afford naphthofuranpyrazol derivatives 4-8. Treatment of 2-[(3-(naphtho[2,1-b]furan-2-yl)-1-phenyl-1H-pyrazol-4-yl)methylene]-malononitrile (4a) with reactants having active hydrogen and Et₃N gave the corresponding pyrazoline, pyran and chromene addition product derivatives 10, 12 and 13, consisting of three different connected heterocyclic moieties. Reaction of 1-((3-(naphtho[2,1-b]furan-2-yl)-1-phenyl-1H-pyrazol-4-yl) methylene)-2-phenylhydrazone (6b) with AcONa and ethyl bromoacetate or chloroacetone afforded the thiazolidinone and methylthiazole derivatives 14 and 15, respectively. In addition, intramolecular cyclization of 6d with Ac₂O afford the corresponding 1,3,4-thiadiazol-2-yl acetamide derivative 16. The structures of the synthesized compounds were confirmed by IR, ¹H-NMR/¹³C-NMR and mass spectral studies. Compound 14 showed promising effects against the tested Gram positive and negative bacteria and fungi.

Anticancer activities, molecular docking and structure–activity relationship of novel synthesized 4 H -chromene, and 5 H -chromeno[2,3- d ]pyrimidine candidates

In the present study, a series of 4H-chromene and 5H-chromeno[2,3-d]pyrimidine derivatives was synthesized and evaluated as potential cytotoxic agents. The cytotoxic activities of the target compounds were evaluated against four cancer cell lines MCF-7, HCT-116, HepG-2, and A549 in comparison with vinblastine and colchicine as reference drugs. We explored the structure–activity relationship of 4H-chromenes with modification at the 2-,4- or 7-position, and fused pyrimidine ring at 2,3-position. Most of the screened compounds showed marginal antitumor activity against the different cell lines in comparison to the standard drugs. The structure–activity relationship study revealed that the antitumor activity of the synthesized compounds was significantly affected by the lipophilicity of the substituent at the 2-,4- or 7-position for the 4H-chromenes, and 5,8-position or fused pyrimidine ring at 2,3-positions for 5H-chromeno[2,3-d]pyrimidines. Structure–activity relationship was elaborated with the help of molecular docking studies. The structures of the synthesized compounds were established on the basis of the spectral data, infrared, proton nuclear magnetic resonance, 13-Carbon nuclear magnetic resonance and mass spectroscopic data.

New bioactive compounds from the marine-derived actinomycete Nocardiopsis lucentensis sp. ASMR2

Abstract In the search for new bioactive compounds from extremophilic actinomycetes, a new marine actinomycete strain, Nocardiopsis lucentensis sp. ASMR2 has been isolated and taxonomically identified from marine plants collected in the Red Sea at Hurghada coasts. A large-scale fermentation of the strain on modified rice solid medium was performed, followed by work-up and purification of the obtained extract using a series of chromatographic purifications, delivering the novel butenolide system 3′-hydroxy-N-(2-oxo-2,5-dihydrofuran-4-yl)propionamide (1a) along with the naturally new 4-methoxy-2H-isoquinolin-1-one (2). Furthermore, eight known bioactive compounds are also reported, namely, indole-3-carboxylic acid, indole-3-acetic acid, indole-3-acetic acid methyl ester, furan-2,5-dimethanol, tyrosol, glycerol linoleate, cyclo-(Tyr, Pro), and adenosine. The chemical structures of the new compounds (1a, 2) were confirmed by extensive one- and two-dimensional (1D and 2D) nuclear magnetic resonance (NMR) spectroscopy, electron ionization high resolution (EI-HR) mass spectrometry, and by comparison with literature data. The antimicrobial activity of the strain extract, as well as of compounds 1a and 2, were studied using a panel of pathogenic microorganisms. The in vitro cytotoxicity of the bacterial extract and compounds 1a and 2 were studied against the human cervix carcinoma cell line (KB-3-1) and its multidrug-resistant subclone (KB-V1).

A Better Journey for Patients, a Better Deal for the NHS: The Successful Implementation of an Enhanced Recovery Program After Renal Transplant Surgery

OBJECTIVES Our aim was to apply the principles of enhanced recovery in renal transplant recipients and to assess the changes in the quality of patient care and patient satisfaction. MATERIALS AND METHODS Our study included 286 consecutive renal transplant patients. Of these, 135 patients went through the enhanced recovery program and 151 patients had traditional recovery. Patient education and discharge planning were commenced on admission. For enhanced recovery, prolonged preoperative fasting was avoided by carbohydrate loading. Goal-directed fluid management was aided by transesophageal Doppler to avoid central line insertion. Intrathecal diamorphine and ultrasonography-guided transversus abdominis plane blocks were used to achieve adequate analgesia. Patients started oral intake a few hours postoperatively. The urinary catheter was removed 2 to 4 days after transplant. RESULTS The postoperative patient-controlled analgesia requirement for morphine was significantly reduced in the enhanced recovery versus traditional recovery group (median of 9.5 vs 47 mg; P < 0.001). The length of stay was significantly reduced for living-donor (median 5 vs 7 days; P < .001) and for deceased-donor transplant recipients (median 5 vs 8.5 days; P < 0.001) with enhanced recovery versus recipients who had traditional recovery. Implementing enhanced recovery saves £2160 per living-donor transplant and £3078 per deceased-donor transplant. In the enhanced recovery group, readmission within 10 days after transplant was 5%. CONCLUSIONS Our service evaluation demonstrated that enhanced recovery benefits both types of renal transplant (living and deceased grafts) procedures, with excellent patient satisfaction and reduction of hospital length of stay.

Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: cytotoxicity and molecular docking investigations

New amide linked bis-indoles 10a, b, and 12 have been synthesized by treatment of tryptamine (9) or 5-aminoindole (11) with oxalyl chloride or adipoyl chloride. In addition, a newly indole derivatives 14–16 incorporated or fused with coumarin moieties have been prepared through the reaction of 9 or 11 with 4-chloro-3-formylcoumarin (13a) or 4-chloro-3-nitrocoumarin (13b). Further, 13-(3-nitrophenyl)-6,13-dihydrochromeno[4,3-b]pyrrolo[3,2-f]quinolin-12(3H)-one (20) has been produced via one-pot Mannish reaction of 11, 4-hydroxycoumarin (17), and 3-nitrobenzaldehyde (18) in the presence of N-chlorosuccinimide (NCS) as a catalyst. A mixture of 3-[(3H-indol-3-ylidene)methyl]-4-hydroxy-2H-chromen-2-one (24A), and 3-[(1H-indol-3-yl)methylene]chroman-2,4-dione (24B) has been obtained with ratio 1:1 through Knoevenagel condensation reaction of indole-3-carboxaldehyde (21) and 17. Structures of the obtained compounds have been assigned by sophisticated spectroscopic techniques (1H-NMR, 13C-NMR, and 2D NMR) and mass spectrometry. All the synthesized compounds have been screened for their cytotoxic activity against the human cervix carcinoma cell line (KB-3-1), where compounds 14a, 16, and 20 exhibit the highest potent activity (IC50 = 1.8, 2.2, and 7.9 µM, respectively) in comparison with the positive control (+)-Griseofulvin (IC50 = 19.2 µM), whereas the tautomeric mixture 24A, B show moderate activity (IC50 = 71.3 µM). Moreover, molecular docking study of the synthesized compounds toward the matrix metalloproteinase-8 (MMP-8) (PDB ID: 1MNC) has also discussed.

Synthesis, biological activity and molecular modeling study of new Schiff bases incorporated with indole moiety

Abstract A new series of heterocyclic Schiff bases 2–9 containing indole moiety were synthesized by facile and efficient condensation of indole-3/2/5-carboxaldehyde (1a/1b/1c) with different aromatic and heterocyclic primary amines using conventional and/or microwave irradiation methods. The structures of the obtained compounds were assigned by sophisticated spectroscopic and spectrometric techniques (1D-NMR, 2D-NMR and MS). The synthesized compounds were screened for their cytotoxicity and antibacterial activities. In vitro cytotoxicity screening revealed that compound 5 exhibited moderate activity against KB-3-1 cell line (IC50=57.7 μM) while 5-indolylimino derivative 7 indicated close to the activity (IC50=19.6 μM) in comparison with the positive control (+)-Griseofulvin (IC50=19.2 μM), while the tested compounds 5, 6b, 7 and 9 revealed good or moderate antibacterial activity. In addition, molecular docking study of Schiff bases 2–9 was performed by Molecular Operating Environment (MOE 2014.09) program on the matrix metalloproteinase-8 (MMP-8) (Protein Data Bank (PDB) ID: 1MNC) in an attempt to explore their mode of action as anticancer drugs.

Synthesis and biological activities of new bis-indole derivatives via microwave irradiation

Abstract Three new series of bis-indole derivatives were synthesized based on p-phenylenediamine (2–4, 5 and 6) and 4,4′-ethylenedianiline moieties (7–9) using facile and efficient condensation of three positional isomeric indole-carboxaldehyde derivatives (1a–c) with bifunctional amines upon microwave irradiation. The symmetric dimeric indole derivatives 2–4 as well as non-symmetric analogues 5 and 6 were obtained by in situ condensation of the respective positional 3-, 2- and 5-isomeric indole-carboxaldehydes with p-phenylenediamine, while compounds 7–9 resulted from respective condensation based on 4,4′-ethylenedianiline. Structures of the obtained compounds were deduced by advanced spectroscopic methods (1H NMR, 13C NMR and MS). In agar diffusion assay, derivative 6 showed moderate antibacterial activity against various Gram positive and negative bacteria, while derivative 7 displayed moderate activity against several Gram positive bacteria. However, in Resazurin assay employing the human cervix carcinoma cell line (KB-3-1), derivatives 2–9 turned out to be inactive.

Synthesis of Some Novel Heterocyclic Compounds Containing Benzofuran Moiety of Potential Antimicrobial Activity

Imidazotriazole, thiazoles, quinoxaline, benzothiazine, imidazo-thiadiazole, imidazopyridine, imidazothiazole were synthesized via reaction of 3-bromoacetyl-5-bromobenzofuran with each of thiourea, phenylthiourea, thiocetamide, thiocarbamoyl pyrazole, o-phenylenediamine, o-aminothiophenol, 2-aminothia-diazole, aminotriazole, 2-aminopyridine and 2-aminothiazole. The structure of the newly synthesized compounds was confirmed by elemental analysis, IR, 1H NMR, and mass spectral data. All compounds were evaluated for their antimicrobial activities, compound 2 gave excellent results.

ANTIMICROBIAL ACTIVITY OF THE REACTION PRODUCTS OF 2-ACETYL- AND 2-(2,2-DICYANO-1-METHYLVINYL)NAPHTHO[2,1-b] FURAN WITH SOME NUCLEOPHILIC AND ELECTROPHILIC REAGENTS

The reaction of 2-acetyl and 2-(2,2-dicyano-1-methylvinyl)naphtho[2,1-b]furan with malononitrile, phenylhydrazine, α-cyanocinnamonitriles, anisaldehyde and other differenet reagents were discussed. The structure of the reaction products were supported by HNMR, CNMR, IR and mass spectra data. The biological activity of the compounds cited in this article were reported.