Hamad A. Al-Khamees

Substituted quinazolines, part 3. Synthesis, in vitro antitumor activity and molecular modeling study of certain 2-thieno-4(3H)-quinazolinone analogs☆

The synthesis of some new 2-thieno-4(3H)-quinazolinone derivatives and their biological evaluation as antitumor agents using the National Cancer Institute (NCI) disease oriented antitumor screen protocol are investigated. Compounds 2-(2-thienylcarbonylamino)-5-iodo-N-(4-hydroxyphenyl)-benzamide (16), 2-(2-thieno)-6-iodo-3-phenylamino-3,4-dihydro-quina-zolin-4-one (26), and 2-(2-thieno)-4-[4-sulfonamidobenzylamino]-6-iodo-quinazoline (42), with GI(50) values of 12.7, 10.3, 16.9 microM, respectively, proved to be the most active members in this study, as compared to the known drug 5-FU. Conformational analysis of the most active molecules using molecular modeling and QSAR techniques enabled the understanding of the pharmacophoric requirements for 2-thieno-quinzolinone derivatives as antitumor agents. These three quinazolinone analogs (16, 26, 42) could be considered as useful templates for future development to obtain more potent antitumor agents.

Photodegradation kinetic study and stability-indicating assay of danazol using high-performance liquid chromatography

A selective high-performance liquid chromatographic procedure for the stability-indicating determination of danazol in the presence of its photolytic degradation products is demonstrated. The photolysis was carried out in glass vials and quartz cell under UV light at 254 nm. Satisfactory results were obtained for the assay and recovery testing with RSD values less than 2%. Kinetic parameters evaluated comprise the order of reaction and the rate constants of the degradation of the danazol irradiated in glass vials or quartz cell.

A Selective Colorimetric Method for the Determination of Penicillins and Cephalosporins with α-Aminoacyl Functions

A simple, sensitive and selective colorimetric method is described for the assay of ampicillin, amoxicillin, cephalexin, cefadroxil and cefaclor in their pharmaceutical preparations. The method is based on measuring the color obtained when the alkaline degradation products of these agents are allowed to react with ascorbic acid. The factors affecting the color generation and determination were studied and optimized. The reaction is selective to β-lactam antibiotics having amino acid side-chains with free amino functions and thus allow interference-free quantitation of some preparations containing these agents in combination with other β-lactam agents. The procedure is also successfully adopted as stability-indicating method for cephalosporins. A tentative mechanism of the color reaction is proposed.

Spectrophotometric Determination of Domperidone Using δA Method

Abstract A spectrophotometric method for the assay of domperidone tablets (Motilium(R)−10 mg) is described. The mean percentage found for the active ingredient per tablet was 100.61 ± 1.19. The drug exhibits maximum absorption at 282 nm in 0.5 N-sulphuric acid and at 294 nm in 0.5 N-sodium hydroxide due to keto-enol tautomerism. δA at 300 nm proved to be linearly related to the drug concentration in the range 5-30 μg ml−1 with a coefficient of variation 1.09%.

Atom level electrotopological state indexes in QSAR: designing and testing antithyroid agents.

AbstractPurpose. To design new antithyroid agents with less side effects, the electrotopological-state (E-state) indexes of thiourylene moiety (SN&S) was utilized as a guideline to develop five acyclic thio-urylene-type compounds with reduced antioxidant property. Methods. These agents were synthesized and screened for antithyroid activity in rats using 125I-thiocyanate discharge technique. In addition, chemiluminescence studies on the activated polymorpho-nuclear leukocytes (PMNLs) were also conducted to reveal antioxidant properties of the tested compounds. Results. A linear relationship between the in vitro literature value of the formation constants of thiourylene-type compounds with iodine (Kc) and the SN&S was observed and utilized in designing those agents. At least one of the compounds (abouthiouzine) was found to have a potential value as an antithyroid agent. The relative efficacy of abouthiouzine [l-n-butyl-3(isonicotinamido)-2-thiourea], after equimolar dose, was 102% and 51.5% of that of propylthiouracil with respect to the rate of 125I-discharge and 125I-uptake, respectively. In addition, Chemiluminescence studies on PMNLs revealed that abouthiouzine has slight oxidant property. Such properties may provide advantages in avoiding the iatrogenic hypothyroidism and antithyroid-induced immunological reactions. Conclusions. The E-state approach provides guidelines to economize efforts and cost of designing new antithyroid drugs.

Synthesis and pharmacological screening of a new series of 3-(4-anti-pyryl)-2-arylthiazolidin-4-ones

Abstract A series of 3-(4-antipyryl)-2-arylthiazolidin-4-one derivatives were synthesized and pharmacologically evaluated for antinociceptive, spasmolytic and cardiovascular activities. The presence of a methoxy-naphthyl or a substituted phenyl group in 2-position of the 4-thiazolidinone ring increased the antinociceptive and spasmolytic activities by 3–12-fold compared with antipyrine. The most potent were the o -methoxy naphthalene and the m -chlorobenzene derivatives. Furthermore, the compounds showed no local anaesthetic activity, but they induced slight decreases in the rabbit arterial blood pressure.

Colorimetric Method for the Determination of Ampicillin and Amoxicillin

A simple colorimetric procedure is described for the quantitation of ampicillin and amoxicillin in their pharmaceutical preparations. The color production is based on the reaction of the oxidation product of ascorbic acid, dehydroascorbic acid, with the corresponding penicillenic acids obtained by the degradation of the antibiotics after heating under acidic conditions. The reaction demonstrated selectivity towards the penicillins having amino acid side chains and thus allowed interference-free quantitation of ampicillin and amoxicillin in combination with cloxacillin or clavulenic acid. The procedure showed good accuracy and precision and offers advantages over the official and many other reported analytical procedures.

1,3,4-THIADIAZOLES. REGIOSELECTIVE O-DEMETHYLATION ON DEHYDRATIVE CYCLIZATION OF 1-(3,4,5-TRIMETHOXYBENZOYL)- 4-SUBSTITUTED THIOSEMICARBAZIDES WITH SULPHURIC ACID

Cyclization of 1-(3,4,5-trimethoxybenzoyl)-4-substituted thiosemicarbazides 2a–g with sulphuric acid at ambient temperature afforded the selectively demethylated products 2-(4-hydroxy-3,5-dimethoxyphenyl)-5-substituted amino-1,3,4-thiadiazoles 4a–g. Meanwhile, dehydrative cyclization of 1-(3,4,5-trimethoxybenzoyl)-4-(benzyl or t-butyl)thiosemi- carbazides 2h, i with sulphuric acid yielded 2-(4-hydroxy-3,5-dimetho xyphenyl)-5-amino-1,3,4-thiadiazole 5. On the other hand, dehydration of 2h, i by heating with phosphorus oxychloride yielded 2-(3,4,5-trimethoxyphenyl)-5-amino-1,3,4-thiadiazole 6.

Colourimetric Determination of Norfloxacin in Tablets By Reaction with p-Benzoquinone

Abstract A simple, quick and sensitive spectrophotometric method based on the combination of norfloxacin and p-benzoquinone at room temperature, apparently by charge-transfer (n → π) mechanism, to yield a 1:1 complex with analytically useful maximum absorption at 495 nm, is described. The estimated molar absorptivity, ∊, and the stability constant, K, are 0.44 × 104 L mol−1 cm−1 and 1.06 × 106 L mol−1 respectively. The role of solvent, p-benzoquinone concentration, pH and presence of water have been investigated. Under the optimized conditions, Beers Law was obeyed over the concentration range 7.5 – 40 μg/ml of norfloxacin. The concentration range of best accuracy deduced from Ringbom plot was 15–40 μ/ml norfloxacin. When the proposed method was applied to the analysis of commercial tablets (Noroxin®), labeled to contain 400 mg of drug per tablet, the mean percentage found was 100.57 ± 1.58 (n = 9). The precision and accuracy of the method proposed have been compared statistically with the official (U.S....

First-derivative spectrophotometric determination of salicylic acid in aspirin

Salicyclic acid has been determined in aspirin powder and tablets by first-derivative spectrophotometry at 316 nm with base-line correction, with a coefficient of variation less than 1%.