AntiHIV, antitubercular and antibacterial activities of novel 1-substituted-3-(3-(4-methylphenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-yl amino) isothioureas

In this research, substituted thiosemicarbazide group was placed at 2nd position & 4-methylphenyl group was placed at 3rd position of condensed pyrimidine nucleus. Entire prepared title analogues were examined for its antibacterial, antitubercular, & anti HIV activities against selected bacteria & virus. The target compounds 1-substituted-3-(3-(4-methylphenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-ylamino)isothioureas (TTS01 – TTS10) were synthesized from 2-hydrazino-3-(4-methylphenyl)benzopyrimidin-4(3H)-one (5) by reacting with various alkyl/aryl isothiocyanates followed by methylation with dimethyl sulphate. Among the test compounds, 2-methyl-3-(3-(4-methylphenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-ylamino)-1-(3-chlorophenyl) isothiourea (TTS09) and 2-methyl-3-(3-(4-methylphenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-yl amino)-1-(4-nitrophenyl) isothiourea (TTS06) shown most potent activity against S. epidermidis, S. Aureus, and P. vulgaris 3 µg/ml MIC. Compounds TTS06 & TTS09 exhibited the antitubercular activity with 12.5 µg/ml MIC and antiHIV activity at 9.06 and 8.56 µg/ml, respectively against HIV1 and HIV2. Thus for further optimization & development of novel antitubercular and antiHIV drugs, compounds TTS06 & TTS09 may act as a pilot derivative.

Methylation of Eugenol Using Dimethyl Carbonate and Bentonite as Catalyst

Eugenol is a compound with a variety of reactive functional groups such as allyl, hydroxy and methoxy. The presence of the functional groups brings eugenol possible to undertake the transformation into various derivative compounds with diverse activities. One of the simple and possible transformations is methylation or alkylation. Commonly, methyl halides and dimethyl sulphate are used as methylation agent. However, those kinds of methylation agents are toxic and carcinogenic. In this research dimethyl carbonate, an alternative methylation agent is used, because of its low toxicity, green, and economic. The synthesis has been carried out by using a catalyst. Bentonite was activated by heating to a temperature using 300 °C. Methylation was shown by the formation of a light yellow liquid (25.71% yield). The structures of products were characterized by GC-MS and obtained a compound, namely bis eugenol (4-allyl-2-methoxyphenoxy) methane (2.37% yield).

Synthesis and Antimalarial Activity of 2-Phenyl-1,10-Phenanthroline Derivative Compounds

To develop new potential antimalarial drugs of 2-phenyl-1,10-phenanthroline 5 derivatives from 8-aminoquinoline as startingmaterial were synthesized in good yields. The synthesis of 2-phenyl-1,10-phenanthroline 5 derivatives compoundswith 8-aminoquinoline 4 as starting material through three steps has been carried out. The first step of reactions is aldolcondensation of benzaldehyde 1 with acetaldehyde 2. The result of reactions is cinnamaldehyde 3 (92.14%) in the form ofyellow solid. The second step of reactions was synthesized of 2-phenyl-1,10-phenanthroline 5 (brown solid, 54.63%)through cyclization of 8-aminoquinoline 4 with cinnamaldehyde 3 compound. The third step of reactions is methylation andethylation of 2-phenyl-1,10-phenanthroline using dimethyl sulphate (DMS) and diethyl sulphate (DES) reagents that it wasrefluxed for 17 and 19 h, respectively. The results of reactions are (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate 6and (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 in yield from 90.62% and 89.70%, respectively. The results oftesting in vitro antiplasmodial activity at chloroquine-resistant Plasmodium falciparum FCR3 strain to 2-phenyl-1,10-phenanthroline 5 derivatives obtained that (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 compound has higherantimalarial activity (IC 50 :0.13 ± 0.02 μM) than antimalarial activity of (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate6 compound (IC 50 :0.25 ± 0.01 μM) and 2-phenyl-1,10-phenanthroline 5 compound (IC 50 :2.45 ± 0.09 μM). While, the resultsof testing in vitro antiplasmodial activity at chloroquine-resistant Plasmodium falciparum D10 strain to 2-phenyl-1,10-phenanthroline 5 derivatives obtained that (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate 6 compound has higherantimalarial activity (IC 50 :0.10± 0.04 μM) than antimalarial activity of (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate7 (IC 50 :0.18 ± 0.01 μM) and 2-phenyl-1,10-phenanthroline 5 compound (IC 50 :0.55 ± 0.07 μM).

SYNTHESIS AND ANTIPLASMODIAL ACTIVITY TESTING OF (1)-N-ALKYL- AND (1)-N-BENZYL-6-NITRO-1,10-PHENANTHROLINIUM SALTS AS NEW POTENTIAL ANTIMALARIAL AGENTS

The synthesis of 5-nitro-1,10-phenanthroline hydrate 2 derivatives from 1,10-phenanthroline monohydrate as starting material has been carried out. The 5-nitro-1,10-phenanthroline hydrate 2 was obtained through nitration reaction using H2SO4 and HNO3 as catalyst and reagent, respectively. Synthesis of (1)-N-alkyl-6-nitro- and (1)-N-benzyl-6-nitro-1,10-phenanthrolinium have been prepared using dimethyl sulphate (DMS), diethyl sulphate (DES), benzyl chloride, benzyl bromine, and benzyl iodide. The reagents of benzyl bromine, and benzyl iodide were synthesized from benzyl chloride using NaBr in ethanol absolute and NaI in acetone, respectively. The five compounds of 5-nitro-1,10-phenanthroline hydrate 2 derivatives were conducted to evaluate the in vitro antiplasmodial activity. The in vitro antiplasmodial was evaluated on strains of Plasmodium falciparum FCR-3 resistant chloroquine and D10 sensitive chloroquine. The 50% inhibition concentration (IC50) of the five compounds ranged from 2.41±1.41 to 0.07±0.01 μM. The results showed that the (1)-N-benzyl-6-nitro-1,10-phenanthrolinium iodide had highest antiplasmodial activity.

Preparation and Characterization of Cationic Emulsion of Styrene and Acrylate

The control of particle size and its distribution has become more and more important both in theory and in practice of emulsion polymerization field. In this study, cationic styrene-acrylate copolymer containing functional monomer was converted into water-soluble polymers by reaction with quaternising agents and acids with the free-soap emulsion polymerization method. The latex was obtained at the existence of nitrogen by the copolymerization of hydrophobic monomer styrene and 2-ethylhexyl acrylate, hydrophilic monomer dimethylaminoethyl methacrylate, modified PVA-0588 as the emulsifiers. The influences of the amount of azoisobutyronitrile initiator, the amount of dimethyl sulphate quaternising agent, reactivity ratio between monomers, charge density and pH value on the preparation process were discussed. The particle size and particle distribution was strongly affected by these factors. The results showed that the latex with narrow particle distribution and mean particle size about 100nm was obtained under redox system by adjusting 33% monomer to become precursor and dropping the rest of 67% monomer, after polymerization, N,N-dimethylamino groups were fully quaternised with dimethyl sulphate to improve the stability of the solutions. The glass temperature of polymer was 58.1°C, as pH values range of solution was 3~5, the stability and charge density of polymer emulsion could improve.