Awwad A. Radwan

Microwave Irradiation-Assisted Synthesis of a Novel Crown Ether Crosslinked Chitosan as a Chelating Agent for Heavy Metal Ions (M +n )

Microwave irradiation was used to obtain a di-Schiff base type crosslinked chitosan dibenzocrown ether (CCdBE) via the reaction between the –NH2 and –CHO groups in chitosan and 4,4′-diformyldibenzo-18-c-6, respectively. The structure of the synthesized compound was characterized by elemental analysis, solid state 13C-NMR and FT-IR spectra analysis. The results showed that the mass fraction of nitrogen in the CCdBE derivative was much lower than those of chitosan. The FT-IR spectra of CCdBE revealed the expected chitosan-crown ether structure, as evidenced by the presence of the characteristic C=N and Ar peaks. The adsorption properties of CCdBE for Pd2+ and Hg2+ were investigated and the results demonstrated that the adsorbent has both desirable adsorption properties with a high particular adsorption selectivity for Hg2+ when in the presence of Pb2+ as well as selectivity coefficients for metal ions of KHg2+/Pb2+ = 8.00 and KHg2+/Pb2+ = 10.62 at pH values of 4 and 6, respectively. The reusability tests for CCdBE for Pb2+ adsorption showed that complete recovery of the ion was possible with CCdBE after 10-multiple reuses while CTS had no reusability at acidic solution because of its higher dissolution. The studied features of CCdBE suggested that the material could be considered as a new adsorbent. It is envisaged that the crosslinking of CTS into CCdBE would enhance practicality and effectiveness of adsorption in ion separation and removal procedures.

Synthesis and Three-dimensional Qualitative Structure Selectivity Relationship of 3,5-Disubstituted-2,4-Thiazolidinedione Derivatives As COX2 Inhibitors

In our effort for synthesis of selective COX2 inhibitors, certain new 2,4-thiazolidinedione derivatives were synthesized. It necessitates preparation of potassium salt of 2,4-thiazolidinedione 2, which condensed with intermediate 4a. The resulting 3-[2-(4-methylphenyl)-2-oxo-1-phenylethyl]-2,4-thiazolidinedione 8 was condensed with appropriate aldehyde to afford compounds 10a, 10i-l, 10o and 10p. Compounds (9a-l, 10a-n, 10p, 11 and 12) were obtained through the preparation of 5-arylmethylidene-2,4-thiazolidinediones 6a-p and reaction of its potassium salt 7a-p with compounds 4a, 4b, and 5. Some compounds displayed significant analgesic activity as compared to reference standards. The anti-inflammatory activity of the synthesized compounds revealed that intermediate 8 and compounds 9c, 10c and 10d showed good results. Compound 10c produced no significant mucosal injury. HipHop methodology of Catalyst program was used to build up hypothetical model of selective COX2 inhibitors followed by fitting the synthesized compounds to this model. Compounds 10c and 10d were suspected to be promising selective COX2 inhibitors. Also, compounds (6c, 8, 9a,c,d,k, 10a,c,d,k, 11 and 12) were docked into COX1 and COX2 X-ray structures, using DOCK6 program. Docking results suggested that several of these derivatives are active COX inhibitors with a significant preference for COX2.

Targeting cancer using cholesterol conjugates

Conjugation of cholesterol moiety to active compounds for either cancer treatment or diagnosis is an attractive approach. Cholesterol derivatives are widely studied as cancer diagnostic agents and as anticancer derivatives either in vitro or in vivo using animal models. In largely growing studies, anticancer agents have been chemically conjugated to cholesterol molecules, to enhance their pharmacokinetic behavior, cellular uptake, target specificity, and safety. To efficiently deliver anticancer agents to the target cells and tissues, many different cholesterol-anticancer conjugates were synthesized and characterized, and their anticancer efficiencies were tested in vitro and in vivo.

Synthesis and antimicrobial activity of certain new 1,2,4-triazolo[1,5-a]pyrimidine derivatives

Certain new derivatives of 1,2,4-triazolo[1,5-a]pyrimidines were synthesized through the reaction of 1,2,4-triazolo[1,5-a]pyrimidine-7-ol with ethyl bromoacetate to afford the ethyl acetate ester, which upon hydrazinolysis gives the corresponding hydrazide. The hydrazide is the key intermediate which was used for the synthesis of the target compounds. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their in vitro antibacterial and antifungal activities. Most of the tested compounds showed comparable results with those of ampicillin and fluconazole reference drugs.

Design and Synthesis of New Cholesterol-Conjugated 5-Fluorouracil: A Novel Potential Delivery System for Cancer Treatment

Cholesterol-conjugated 5-fluorouracil prodrugs were designed to be carried in vivo via low density lipoproteins (LDL) and subsequently undergo LDL-receptor-mediated internalisation into cancer cells. In vivo anti-cancer evaluation was performed using 5-fluorouracil-cholesterol conjugate in a mouse model. The obtained prodrugs were more potent than 5-fluorouracil control drug at the same 5-fluorouracil content (3 mg·kg−1).

Schiff bases of indoline-2,3-dione (isatin) with potential antiproliferative activity

BackgroundCancer is one of the most dreaded diseases and it is a leading cause of mankind death worldwide. Recent reports documented a remarkable antiproliferative activity of isatin nucleus against various cancer cell lines. The current work describes the antiproliferative activity of Schiff bases of combinatorial mixtures of the isatin derivatives M1-M22 as well as the individual compounds 1-11(A-K) of these combinatorial mixtures.ResultsThe designed combinatorial library composed from eleven hydrazides A-K and eleven isatin derivatives 1-11 has been synthesized to formally generate 22 mixtures, M1-M22 of 121 Schiff bases, and their antiproliferative activity against K562 chronic myelogenous leukemia cells was evaluated. The indexed method of analysis of the prepared library was applied to elucidate the active components in the tested mixtures M1-M22. The predictions from the crossing procedure was validated through evaluation of the antiproliferative activity of individual compounds 1-11(A-K) of the library. Individual compounds 1-11(A-K) were also evaluated against the non-tumorigenic MCF-12A cell line to investigate their selectivity. A pharmacophore model was developed to further optimize the antiproliferative activity among this series of compounds.ConclusionsVariable antiproliferative activity was revealed with the investigated mixtures M1-M22 and the individual compounds 1-11(A-K). Most of the tested mixtures and several individual Schiff bases displayed high potency with IC50 values in the low micromolar range. A considerable selectivity of some individual compounds to the tumorigenic K562 cell line compared with the non-tumorigenic MCF-12A cell line was observed as indicated by their selectivity index (SI).

Synthesis and pharmacophore modeling of novel quinazolines bearing a biologically active sulfonamide moiety

In the present work, interaction of the strategic starting material, methyl 2-isothiocyanatobenzoate (1), with sulfa drugs resulted in the formation of methyl 2-[3-(4-(N-substituted sulfamoyl)phenyl)thioureido] benzoates 2-5, which upon reaction with hydrazine hydrate afforded N-amino derivatives 6-9. Triazoloquinazoline derivatives 10-18 were obtained via reaction of compounds 6-8 with aromatic aldehydes. Also, the reaction of compound 8 with formic acid gave the corresponding triazoloquinazoline derivative 19. Triazinoquinazoline derivatives 22, 23 were obtained via reaction of N-amino derivatives 6 or 8 with ethyl chloroacetate. Interaction of 6 with diethyloxalate yielded triazoloquinazoline 26. The synthesized compounds were screened for their in vitro antimicrobial activities and some of them exhibited promising antibacterial activity compared to ampicillin as positive control. Compounds that revealed significant activity are able to satisfy effectively the proposed pharmacophore geometry.

Pharmacophore Elucidation and Molecular Docking Studies on 5-Phenyl- 1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic Acid Derivatives as COX-2 Inhibitors

A set of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic acid derivatives (16–32) showing anti-inflammatory activity was analyzed using a three-dimensional qualitative structure-selectivity relationship (3D QSSR) method. The CatalystHipHop approach was used to generate a pharmacophore model for cyclooxygenase-2 (COX-2) inhibitors based on a training set of 15 active inhibitors (1–15). The degree of fitting of the test set compounds (16–32) to the generated hypothetical model revealed a qualitative measure of the more or less selective COX-2 inhibition of these compounds. The results indicate that most derivatives (16, 18, 20–25, and 30–32) are able to effectively satisfy the proposed pharmacophore geometry using energy accessible conformers (Econf < 20 kcal/mol). In addition, the triazole derivatives (16–32) were docked into COX-1 and COX-2 X-ray structures, using the program GOLD. Based on the docking results it is suggested that several of these novel triazole derivatives are active COX inhibitors with a significant preference for COX-2. In principle, this work presents an interesting, comprehensive approach to theoretically predict the mode of action of compounds that showed anti-inflammatory activity in an in vivo model.

Potential of lipid nanoemulsion for drug delivery of cholesteryl-hexahydrophthaloyl-5-fluorouracil

The present study was undertaken to evaluate lipid nanoemulsions of cholesteryl-hexahydrophthaloyl-5-fluorouracil (CHHP-5-FU) to improve its therapeutic potential and to reduce adverse effects. CHHP-5-FU-loaded lipid nanoemulsions were prepared by high energy emulsification method and evaluated for droplet size, polydispersity index, zeta potential, refractive index and drug release. The drug release was found to be increased significantly by increasing the concentration of surfactants and decreasing droplet size & viscosity of formulations (P

Formulation and evaluation of cholesterol-rich nanoemulsion (LDE) for drug delivery potential of cholesteryl-maleoyl-5-fluorouracil

Abstract It has been reported that cholesterol-rich nanoemulsions (LDE) can bind to low density lipoprotein (LDL) receptors which can concentrate anticancer drugs in the tissues via LDL receptor overexpression and reduced the adverse effects of the treatment. Therefore, in this study, LDE nanoemulsions of cholesteryl-maleoyl-5-fluorouracil (5-FU conjugate) were developed and evaluated in vitro. LDE nanoemulsions were prepared by high-energy emulsification technique. Developed formulations were characterized in terms of droplet size, polydispersity index, zeta potential, viscosity and refractive index. Optimized formulation (L5) was also evaluated for surface morphology using transmission electron microscopy (TEM). Developed formulations were subjected to in vitro drug release studies through dialysis membrane. The droplet size (50 nm), polydispersity index (0.109) and viscosity (32.16 cp) were found to be lowest for optimized formulation L5. The results of zeta potential indicated the stable formation of developed LDE nanoemulsions. TEM images of optimized formulation indicated non-spherical shape of droplets. About 97% of conjugate was found to be released from L5 after 24 h of study. Overall, these results indicated that developed LDE nanoemulsions could be successfully used for oral delivery of 5-FU conjugate.