Haythem A. Saadeh

Synthesis of novel hybrid molecules from precursors with known antiparasitic activity.

Three novel new compounds derived from antiparasitic precursors have been synthesized and tested for their antiamoebic and antigiardial activities. The condensation of 2-(2-methyl-5-1H-nitroimidazolyl)ethylamine (6) with 5-nitro-2-furylacrylic acid (7) gave 3-(5-nitrofuran-2-yl)-N-[2-(5-nitroimidazol-1-yl)ethyl]acrylamide (8). Condensation of 7 with 7-chloro-4-(piperazin-1-yl)quinoline (9) afforded 1-[4-(7-chloroquinolin-4-yl)piperazin-1-yl)-3-(5-nitrofuran-2-yl)propenone as a mixture of two isomers; 10-a (the E-isomer) and 10-b (the Z-isomer). In addition, the reaction of 9 with 1-(2-bromoethyl)-2-methyl-5-nitroimidazole (11) in the presence of K2CO3 and NaI yielded 7-chloro-4-(4-[2-(5-nitroimidazol-1-yl)ethyl]-piprazin-1-yl)quinoline (12). On the basis of preliminary screening data for these new compounds, compound 12 exhibited potent lethal activities against Entamoeba histolytica and Giardia intestinalis; its IC50 ( about 1 µM) was lower, at least by a factor of five, compared to the standard drug, metronidazole. In addition, the IC50 of compound 12 against the tested parasites is 600 times below that against Hep-2 and Vero cells. Compounds 8 and 10-a also exhibited potent or moderate antiamoebic and antigiardial activities with IC50 values of about 5.5 µM, and 140 µM, respectively, against the tested parasites. These two hybrid molecules, 8, 10-a, were also non-cytotoxic at the lethal concentrations against the parasites.

Highly stable, functionalized polyimides for second order nonlinear optics

This paper summarizes our research effort in developing polyimides functionalized with nonlinear optical chromophores for applications in second order nonlinear optical devices. In the past several years, we have developed several general synthetic approaches to these materials. Detailed physical characterization indicated that these materials are quite promising in stabilizing the dipole orientation. Large optical nonlinearity was observed in a few of the systems in which a NLO chromophore exhibiting large µβ value was incorporated. However, a synthetic challenge is to incorporate those NLO chromophores exhibiting better µβ values into polyimide backbones because of the sensitivity of these chromophores towards chemical manipulation. A possible solution by utilizing palladium catalyzed coupling reaction is discussed and an example presented.

New Synthesis and Antiparasitic Activity of Model 5-Aryl-1- methyl-4-nitroimidazoles

A number of 5-aryl-1-methyl-4-nitroimidazoles 5a-f have been synthesized in good yields by the Suzuki coupling reaction between 5-chloro-1-methyl-4-nitroimidazole (3) and arylboronic acids 4a-f, aided by dichlorobis-(triphenylphosphine)palladium(II), K2CO3, and tetrabutylammonium bromide in water at 70-80 °C. Compounds 5a-f were characterized by elemental analysis, NMR and MS spectral data. On the basis of in vitro screening data, 5-(3-chlorophenyl)-1-methyl-4-nitro-1H-imidazole (5f) exhibited potent lethal activity against Entamoeba histolytica and Giardia intestinalis with IC50 = 1.47 µM/mL, a value lower by a factor of two than that of the standard drug, metronidazole. The boosted activity of 5f was not accompanied by any increased cytotoxicity. The rest of the series also exhibited potent antiparasitic activity with IC50 values in the 1.72-4.43 µM/mL range. The cytotoxicity of the derivatives 5c and 5e was increased compared to the precursor compound, metronidazole, although they remain non-cytotoxic at concentrations much higher than the antiparasitic concentration of the two derivatives.

Heterocycles from Nitrile Imines. Part III. Substituent Effect on Ring-Chain Tautomerism of 1,2,3,4-Tetrahydro-s-tetrazines

Selected series of 6-substituted 4-aryl-3-heteroaryl-1-methyl-1,2,3,4-tetrahydro-s-tetrazinea (V:1-12) were synthesized via direct interaction between appropriate nitrile imine and model methylhydrazonea. The extent of «ring-chain» tautomerism, as evidenced from nmr spectral data of V, is dependent on the nature of substituents at N-4, C-3, and C-6. The results reveal that: (i) The concentration of the cyclic tautomer tends to decrease as the basicity of the arylated N-4 decreases

A new family of amorphous molecular materials showing large photorefractive effect

A novel series of amorphous molecular materials containing carbazole and methine dyes have been synthesized and characterized for photorefractive applications.

Hybrid Drugs as Potential Combatants Against Drug-Resistant Microbes: A Review

Antimicrobial resistance to drugs is a serious threat to public health. Different strategies have been adopted to deal with antimicrobial resistance to known drugs, one such strategy is the use of drug hybrids; this is a promising strategy to address the growing problem of drug resistance. The present review covers the very recent examples of combining (hybrid) two standard drugs in a single molecule for combating antibiotic-resistant microorganisms, and to present evidence supporting that drug hybrids are the urgent and practical solution to stop or slow down the spread of drug resistance. In addition, this review provides a literature overview of antimicrobial hybrids of standard drugs and their impact on antimicrobial resistance, covering publications between 2015 and 2016.

In Vitro Activity of Novel Metronidazole Derivatives on Larval Stages of Echinococcus Granulosus

The effects of metronidazole (MTZ) and novel synthesized MTZ derivatives on in vitro cultured Echinococcus granulosus protoscoleces (PSCs), 30 day old segmentation stage and hydatid cysts (HC) developing secondarily in BALB/c mice were compared to those caused upon treatment with comparable doses of albandazole (ABZ) and mebendazole (MBZ) drugs. The highest protoscolicidal action resulted from the use of a non-schiff based MTZ derivative (MTZ-w: 4-[2-(2-methyl-5nitro-1H-imidazol-1-yl) ethyoxy] benzeyldehyde). Incubation of PSCs with MTZ-w concentrations of 25, 12.5 and 6.25 µg/ml resulted in significantly higher mortality rates than those caused by ABZ or MBZ at all periods post incubation. Total mortality of PSCs always occurred one day earlier using MTZ-w. Moreover, incubation of PSCs with MTZ-w at 6.25 µg/ml concentration resulted in greater mortality of PSCs than that caused by ABZ at 25ug/ml concentration. Three other MTZ derivatives showed similar in vitro effects on PSCs to those caused by ABZ or MTZ. Light microscopy revealed that changes in PSCs exposed to MTZ derivatives and ABZ reflected their relative actions in targeting scolex hooks, suckers and tegument. MTZ-w and ABZ caused rupture of hooks, deformation in suckers and disintegration in tegument of both PSCs and in vitro cultured segmentation stage. Less detrimental changes occurred upon the exposure to other MTZ derivatives. Exposure of HC to MTZ-w and ABZ caused regression in their size, damage in germinal membrane, fragmentation of underlining tissue, and scaling of laminated membrane. MTZ-w warrants further assessment as a potential chemotherapeutic drug against cystic echinococcosis in both animals and humans.

1-Benzyl-5-methoxycarbonylmethylthio-4-nitroimidazole

Molecules of the title compound, methyl 1-benzyl-4-nitro-5-imidazolylthioacetate, C 13 H 13 N 3 O 4 S, can be viewed as an arrangement of three intersecting planes of atoms. The plane of the imidazole ring and its bonded atoms (r.m.s.d. = 0.030 A) intersects the plane of the benzyl group (r.m.s.d. = 0.004 A) at an angle of 89.0 (5)°. The plane of atoms extending from the S atom to the methyl group (r.m.s.d. = 0.004 A) intersects the first two planes at angles of 85.9 (5) and 15.2 (5)°, respectively. The imidazole ring is twisted about the S-C3(ring) bond so that the C11-S-C3-N1 (ring) torsion angle is obtuse. The conformation of the chain of atoms from the imidazole ring to the benzyl group is nominally trans, while that to the thioacetate is gauche