Tahsin M. Al-Nakib

Benzylideneindanones and Benzylidenebenzosuberones: Relationship between Structure, Antimycotic Activity and Acute Toxicity

A series of E-2-benzylidene-1-indanones and E-2-benzylidene-1-benzosuberones were synthesized to investigate their in vitro antifungal activity ag

The in vitro Antimycotic Activity and Acute Toxicity of Third-Generation Bezylidenetetralones and Heteroarylidenetetralones

Objectives: A new series of E-2-arylmethylene-1-tetralones and E-2-heteroarylmethylene-1-tetralones (third generation) were designed as potential antimycotic agents against human pathogenic yeasts. Methods: The new compounds were obtained by aldol condensation of 1-tetralone with the appropriately substituted aldehydes in either acid- or base-catalysed conditions. These compounds were tested for their in vitro antimycotic activity against 24 strains of Cryptococcus neoformans, Candida spp. and Trichosporon cutaneum by a microtitre well technique in a liquid casitone medium, using a double dilution method. The toxicity of the new compounds was determined in vitro in cultured HeLa cells, in HeLa growth medium and in vivo in MFI mice. Results: Nineteen new E-2-benzylidine-1-tetralones were prepared, and 16 of the tested compounds showed superior antimycotic activity when compared to the first-generation E-2-benzylidine-1-tetralones synthesised previously. Twelve of these third-generation compounds were more active against different strains of yeasts than 6 commercial antimycotic agents similarly tested. An in vitro toxicity study and an in vivo acute toxicity study in MFI mice showed that these compounds were severalfold less toxic than most of the commerical antimycotics, with 4 being comparable to or less toxic than the least toxic of the commercial agents (amphotericin B) tested by the same procedures. Conclusions: Twelve members of this new E-2-benzylidine-1-tetralone class of compounds are promising candidates for antimycotic agents worthy of further investigation.

On substance abuse in Kuwait (1992–1997): Evidence from toxicological screening of patients

PURPOSE To assess preference for different psychoactive substances and time trends in Kuwait. METHODS Analysis of urine and blood samples of specimens sent by attending physicians to the only public health reference laboratory for toxicological screening in the country. RESULTS A total of 28,548 tests were performed on 3781 samples. Cannabinoids were positive in 40% of the tested samples, opiates in 24%, ethanol in 10%, and amphetamines in 5%. Elevated concentrations of methadone, cocaine, and phencyclidine did not exceed 0.1%. About 40% of samples was positive for benzodiazepines, but their therapeutic use obscures the informativeness of this finding. There was a significant increase in the proportion of positive results for ethanol, amphetamines, and benzodiazepines. IMPLICATIONS It is high time to implement a modern and comprehensive preventive and control program. The tendency to blame the Iraqi invasion for drug addiction has hampered efforts to recognise and address the problem in its entirety.

An Evaluation of the Acute in Vivo Toxicity of Benzylidenechroman-4-Ones, L-Thiobenzylidenechroman-4-Ones and Benzylidenetetralones

A series of new compounds were evaluated for acute in vivo toxicity. Their synthesis and antifungal activity have previously been described by us. The naturally occurring class of compounds to which they belong - the benzylidenechroman-4-ones - have been identified as a potential source of new antifungal agents. These compounds were found to be less toxic, as judged by acute toxicity, than existing commercially available antifungals. A number of conclusions can be drawn about the relationship of structural changes in this series of compounds to increases or decreases in acute toxicity.

Structure-to-Antimycotic Activity of Benzylidenechromanones against 6 Miconazole-Resistant Pathogenic Yeasts in vitro

Fifty-five new compounds belonging to the naturally occurring benzylidenechromanones were synthesised and their activity against the important human pathogenic yeasts Cryptococcus neoformans, Candida

Antimycotic Activity and Acute Toxicity of Benzopyranopyrans and Related Compounds

A series of 39 new benzopyranopyrans and related compounds were synthesised and their antimycotic activity in vitro was evaluated against 4 species of human pathogenic yeasts which were insensitive to miconazole, isoconazole and tolnaftate. The minimum inhibitory concentrations (MICs) of these commercial compounds ranged between 50 and 150 µg/ml. Of the new compounds, 15 were active against 5 strains of Cryptococcus neoformans, while 9 more were active against 3 of these strains with an MIC of 6 µg/ml or lower. Similar MICs were shown by 5 compounds which were active against Candida albicans and 3 which were active against Trichosporon cutaneum. All the active compounds were found to be less toxic than the 3 commercial antimycotics, as judged by their LD50 values in mice. A number of deductions were made regarding the structural variations which resulted in the heterogeneity of response shown by the strains of C. neoformans tested in this series.