Theophylline Derivatives' In-vivo Analgesic and Anti-Inflammatory Activities

The reaction of theophylline and chloro-acetyl chloride produced an exceptional series of substituted theophylline derivatives (3A-3D), followed by ammonium thiocyanate and substituted aromatic aldehyde, and these synthesized derivatives were screened to study their analgesic and anti-inflammatory activities. UV, IR, H-1 NMR, mass spectral data, and CHN activities were used to describe the compounds, which were shown to be considerably efficacious at 100 mg/kg p.o., as well as experimental results that were statistically significant at the p <0.01 and p <0.05 levels.

Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung Cancer

Chemotherapy is the most common clinical treatment for non-small cell lung cancer (NSCLC), but low efficiency and high toxicity of current chemotherapy drugs limit their clinical application. Therefore, it is urgent to develop hypotoxic and efficient chemotherapy drugs. Theophylline, a natural compound, is safe and easy to get, and it can be used as a modified scaffold structure and hold huge potential for developing safe and efficient antitumor drugs. Herein, we linked theophylline with different azide compounds to synthesize a new type of 1,2,3-triazole ring-containing theophylline derivatives. We found that some theophylline1,2,3-triazole compounds showed a good tumor-suppressive efficacy. Especially, derivative d17 showed strong antiproliferative activity against a variety of cancer cells in vitro, including H460, A549, A2780, LOVO, MB-231, MCF-7, OVCAR3, SW480, and PC-9. It is worth noting that the two NSCLC cell lines H460 H and A549 are sensitive to compound d17 particularly, with IC50 of 5.929 ± 0.97 μM and 6.76 ± 0.25 μM, respectively. Compound d17 can significantly induce cell apoptosis by increasing the ratio of apoptotic protein Bax/Bcl-2 by downregulating the expression of phosphorylated Akt protein, and it has little toxicity to normal hepatocyte cells LO2 at therapeutic concentrations. These data indicate that these theophylline acetic acid-1,2,3-triazole derivatives may be potential drug candidates for anti-NSCLC and are worthy of further study.

Design, synthesis, biological evaluation and molecular docking of 1,7-dibenzyl substituted theophylline derivatives as novel BRD4-BD1 selective inhibitors

Bromodomain-containing protein 4 ( BRD4 ), an epigenetic reader, has been recognized as a target with therapeutic potential in several types of cancer and cardiovascular diseases. In this study, a series of 1,7-dibenzyl substituted theophylline derivatives were synthesized and their BRD4 inhibitor activities were evaluated. Most of the compounds showed detectable activities with IC 50 values in the range of 2.51–10.50 µM. Therein, compound 6e showed significant selectivity for two bromodomains of BRD4, the inhibition of BD1 ( IC 50 = 2.51 µM ) was 20 times greater than that of BD2 (IC 50 > 50 µM). Similarly, compounds 6b – 6d, 6f, 6j and 8a also displayed favorable BRD4-BD1 selectivity. In addition, molecular docking of compound 6e was performed to predict conceivable binding patterns of it with BRD4, prompting residue Ile146 might be crucial to the observed selectivity of BRD4-BD1. These findings will be of great value and significance for the development of novel BRD4-BD1 inhibitors.

Adsorption and corrosion inhibition behaviour of new theophylline–triazole-based derivatives for steel in acidic medium

The design and synthesis of a series of theophylline derivatives containing 1,2,3-triazole moieties are presented. The corrosion inhibition activities of these new triazole–theophylline compounds were evaluated by studying the corrosion of API 5 L X52 steel in 1 M HCl medium. The results showed that an increase in the concentration of the theophylline–triazole derivatives also increases the charge transference resistance ( R ct ) value, enhancing inhibition efficiency and decreasing the corrosion process. The electrochemical impedance spectroscopy under static conditions studies revealed that the best inhibition efficiencies (approx. 90%) at 50 ppm are presented by the all-substituted compounds. According to the Langmuir isotherm, the compounds 4 and 5 analysed exhibit physisorption–chemisorption process, with exception of the hydrogen 3 , bromo 6 and iodo 7 substituted compounds, which exhibit chemisorption process. The corrosion when submerging a steel bar in 1 M HCl was studied using SEM-EDS. This experiment showed that the corrosion process decreases considerably in the presence of 50 ppm of the organic inhibitors. Finally, the theoretical study showed a correlation between E HOMO , hardness ( η ), electrophilicity (W), atomic charge and the inhibition efficiency in which the iodo 7 substituted compound presents the best inhibitor behaviour.