Medicinal Chemistry

The tetralone analogues of podophyllotoxin were synthesized by the chalcone route. This route attracts the attention because of its simple operating conditions and easy availability of the chemicals. Initially, chalcones were prepared in high yields by Claisen-Schmidt reaction of acetophenones derivatives with 3,4,5-trimethylthoxybenzaldehyde. The cyclopropyl ketones were prepared in good yields by Simmon-Smith reaction of chalcones with diiodomethane with Zn-Cu couple in presence of ether. Tetralones were prepared in good yields by the intramolecular cyclization reaction of cyclopropyl ketones in the presence of p-toluene sulphonic acid and acetic anhydride. The structures of the synthesized compounds were confirmed by IR, 1H NMR and Mass spectral technique. The title compounds were screened for their antimitotic and antimicrobial activities.

Conducting polymers (CPs) were first fabricated in the 70s of XX century as a novel generation of organic materials that have both electrical and optical properties similar to those of metals and inorganic semiconductors. The fact that several tissues are responsive to electrical fields and stimuli has made CPs attractive for a number of biological and medical applications. This review provides information on desirable CP properties specific to biomedical applications and how CPs have been optimized to generate these properties. The manuscript first introduces different types of CPs, their unique properties and their synthesis. Then specific information is provided on their modification for use in applications such as biosensors, medical engineering, and also neural probes.

The chemical constituents of the essential oils extracted from Artemisia giraldii and Artemisia rubripes were analyzed by GC-MS. The bioactivities of two essential oils against Tribolium castaneum and Lasioderma serricorne were investigated. The main constituents in A. giraldii essential oil were 1,8-cineole (40.72%), camphor (22.50%), terpinen-4-ol (12.41%) and α-terpineol (4.14%). β-Farnesene (12.23%), 1,8-cineole (11.09%), β-caryophyllene (10.68%), germacrene D (10.01%), camphor (7.01%) were principal constituents in A. rubripes essential oil. The essential oil of A. giraldii possessed contact and fumigant toxicities (LD50=23.72 μg/adult and LC50=16.78 mg/l air, respectively) against T. castaneum adults. In addition, the essential oil of A. giraldii possessed contact and fumigant toxicities (LD50=8.88 μg/adult and LD50=5.41 mg/l air, respectively) against L. serricorne adults. The essential oil of A. rubripes showed contact and fumigant toxicities (LD50=16.18 μg/adult and LD50=25.10 mg/l air, respectively) against L. serricorne adults, and the very low contact and fumigant toxicities against T. castaneum. The results indicated that the essential oil of A. giraldii had the potential to be developed as insecticide for control of T. castaneum and L. serricorne.

Clenbuterol is a sympathomimetic amine used for breathing disorders as a decongestant and bronchodilator. During the process development of clenbuterol, the process related impurity bromoclenbuterol was identified as a critical impurity along with the final API. The present work describes the synthesis and characterization of this bromoclenbuterol.

Some new 2-(substituted)-N-(6-bromo-4-oxo-2-phenylquinazolin-3(3H)-yl) acetamides (4.1-9), 2-(substituted)- N-(6,8-dibromo-4-oxo-2-phenylquinazolin-3(3H)-yl) acetamides (4.10-18), 2-(substituted)-N-(6-chloro-4-oxo-2- phenylquinazolin-3(3H)-yl) acetamides (4.19-27) and 2-(substituted)-N-(6,8-dichloro-4-oxo-2-phenylquinazolin- 3(3H)-yl) acetamides (4.28-36) were synthesized in good yield and investigated for analgesic activity. Computer aided drug design (CADD) studies were performed to rationalize the best fitting value of the prepared compounds. All the test compounds exhibited significant analgesic activity compared to reference standard diclofenac sodium. The compounds with aliphatic group (CH3 or C2H5) (4.1, 2, 10, 11, 19, 20, 28 and 29) showed most potent analgesic activity of the series and it is moderately more potent compared to the reference standard diclofenac sodium.

The antimicrobial activities of crude extracts and fractions from three Baccharis L. species were tested against Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8738), Pseudomonas aeruginosa (ATCC 9027), and Candida albicans (ATCC 10231) using the microdilution plate method. The results showed that the crude extract from female B. burchellii Baker had moderate activity against S. aureus (minimum inhibitory concentration [MIC], 0.9 mg.mL-1). Among the fractions obtained from this extract, the dichloromethane fraction showed the highest activity against S. aureus (MIC, 0.4 mg.mL-1). The ethyl acetate fractions from female B. burchellii (MIC, 0.6 mg.mL-1 and 1.2 mg.mL-1, respectively) and B. aracatubaensis Malag (MIC, 1.1 mg.mL-1 for both) were moderately effective against S. aureus and P. aeruginosa. The extracts from B. organensis Baker showed no significant activity against any organism tested. None of the extracts from Baccharis species showed any activity against C. albicans. In addition, the chemical investigation of the dichloromethane and ethyl acetate fractions from female B. burchellii was carried out, resulting in the identification of trans-ferulic acid, ethyl caffeoate, naringenin, and 7-hydroxy-benzaldehyde compounds. These phenolic compounds were found in other species of Baccharis and have been shown to possess antimicrobial activity. The results obtained in this work with respect to B. burchellii indicate that this species is a promising source of compounds with antimicrobial activities.