Antihelminthic activity of some newly synthesized 5(6)-(un)substituted-1H-benzimidazol-2-ylthioacetylpiperazine derivatives

Piperazine derivatives of 5(6)-substituted-(1H-benzimidazol-2-ylthio)acetic acids were synthesized by using two methods and studied for antihelminthic activity. The antiparasitic screening showed that compounds 18-24 exhibited higher activity against Trichinella spiralis in vitro in comparison to methyl 5-(propylthio)-1H-benzimidazol-2-yl-carbamate (albendazole). Most active were compounds 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-1H-benzimidazole 21 and 2-{[2-oxo-2-(4-benzhydrylpiperazin-1-yl)ethyl]thio}-5(6)-methyl-1(H)-benzimidazole 19 as well as 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-5(6)-methyl-1(H)-benzimidazole 23 with efficacy of 96.0%, 98.4% and 100%, respectively. The tested derivatives 15-19 and 20-23 were less active against Syphacia obvelata in vivo than albendazole and exhibited the same efficacy as piperazine, but in twice lower concentration.Compounds 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-1H-benzimidazole 21, 1,4-bis[(5(6)-methyl-1(H)-benzimidazol-2-ylthio)acetyl]piperazine 17 and 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-5(6)-methyl-1(H)-benzimidazole 23 had higher efficacies of 73%, 76%, and 77%, respectively.     

Reduction mammaplasty for symptomatic macromastia: which factors influence the post-operative outcome?

Purpose

We evaluated the long-term results and patient’s satisfaction in reduction mammaplasties for symptomatic mammary hypertrophy.

Methods

From 2002 to 2008 a total of 92 women underwent bilateral mammaplasty for a symptomatic macromastia at our department. Three different surgical techniques for reduction mammaplasty were used (Bostwick, Stroembeck, Ribeiro). Patients were re-contacted in 2009 and asked to complete a self-assessment survey in order to asses their satisfaction with the post-operative symptom-relief and the overall outcome.

Results

90.5 % of all patients stated, that they would retrospectively re-opt for a reduction mammaplasty. Preoperative patients' age, BMI and severity of macromasty-related symptoms were found to be factors positively correlated with a high post-interventional satisfaction with the achieved symptom-relief and the overall outcome. No correlation was found between the amount of intra-operatively resected breast tissue and the post-operative patients’ assessment. Patients’ assessment regarding the achieved post-operative symptom relief was comparable for all three surgical techniques, however the overall outcome rating for both bi-pedicled approaches (Stroembeck and Ribeiro) was higher compared to the mono-pedicled Bostwick technique.

Conclusions

Reduction mammaplasty for patients with a mammary hypertrophy and somatic symptoms could offer a causal and effective treatment. The predictive factors for a high patients’ satisfaction identified in this study could become a valuable tool in the pre-operative patients counceling and their role should be further evaluated prospectively. The use of bi-pedicled surgical techniques seems to favor a high post-operative patients’ assessment.     

Synthesis, characterization and cytotoxicity of some novel 1,3-disubstituted-2,3-dihydro-2-iminobenzimidazoles

Some new 1,3-disubstituted-2,3-dihydro-2-iminobenzimidazoles were synthesized using 1-(un)substituted-2-aminobenzimidazoles as precursors in order to determine their cytotoxicity. The structures of the compounds were confirmed by IR, ¹H NMR, ¹³C NMR and elemental analysis.Compounds 4, 7-11 and 13-14 were evaluated for their cytotoxical effect on two cancer cell lines: human colorectal cancer cell line HT-29, breast cancer cells MDA-MB-231 and as well as normal spleen cells. The distinctly marked antiproliferative activity of 1,3-bis(3-phenylpropyl-1)-1,3-dihydro-2H-benzimidazol-2-imine hydro bromide 7, N-(aminopropyl)-2-(3-{2-[(aminopropyl)-amino]-2-oxoethyl}-2-imino-2,3-dihydro-1H-benzimidazol-1-yl)acetamide 9 and 1,3-bis[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-2,3-dihydro-2H-benzimidazol-2-imine 11 against human colorectal cancer cell line HT-29 was ascertained and the calculated IC₅₀ were 9.26, 0.56 and 0.013 nM respectively. Compounds 4, 9, 10 and 13 exhibited relative high cytotoxic activity against MDA-MB-231 cells. The calculated IC₅₀ values were in the range 0.123-1.65 nM. All tested compounds excluding compound 1,3-bis[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-2,3-dihydro-2H-benzimidazol-2-imine (11) revealed proliferative activities to normal spleen cells. The computed EC₅₀ values varied from 0.05 to 16.91 nM.     

Synthesis, antitrichinnellosis and antiprotozoal activity of some novel thieno[2,3-d]pyrimidin-4(3H)-ones containing benzimidazole ring

Some novel thieno[2,3-d]pyrimidin-4(3H)-ones containing benzimidazol-2-yl-thioethyl- and benzimidazol-2-yl-methanethioethyl moiety in second position of the pyrimidine ring were synthesized in order to determine their antitrichinellosis and antiprotozoal effects. The structures of the compounds were confirmed by IR, (1)H NMR and elemental analysis. The antiparasitic screening showed that the benzimidazole derivatives of thieno[2,3-d]pyrimidin-4(3H)-ones exhibited higher activity against Trichinella spiralis in vitro in comparison albendazole. The most active compound, 2-[2-(5-nitro-1H-benzimidazol-1-yl)ethyl]-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one 22 revealed 95% activity at a dosage of 5?mg/kg?mw after 24?h, while compounds 8 and 10 applied at the same dose showed efficacy of 90% after 48?h. The compound 2-{2-[(5(6)-nitro-1H-benzimidazol-2-yl)thio]ethyl}-5,6,7,8-tetrahydro[1]-benzothieno[2,3-d]pyrimidin-4(3H)-one 11 exhibited 90% efficacy after 24?h. The pharmaco-therapeutic study in vivo on invaded with Lamblia muris white mice showed 100% effectiveness of the compounds 8, 10, 11, 13-15 and 22, 23 after five-days-treatment course.     

Benzo[4,5]thieno[2,3-d]pyrimidine phthalimide derivative,one of the rare noncompetitive inhibitors of dipeptidyl peptidase-4

A small library of benzo[4,5]thieno[2,3-d]pyrimidine phthalimide and amine derivatives was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4). The phthalimide derivatives exhibited better activity than the amine precursors, with 2-(2-(3-chlorobenzyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)isoindoline-1,3-dione (compound 14 ) as the most effective inhibitor (IC₅₀ = 34.17 ± 5.11 μM). The five most potent selected inhibitors did not show cytotoxicity to a greater extent on Caco-2 cells, even at a concentration of 250 μM. Compound 14 is considered as a novel representative of the rare noncompetitive DPP-4 inhibitors. Molecular docking and dynamics simulation indicated the importance of the Tyr547, Lys554, and Trp629 residues of DPP-4 in the formation of the enzyme–inhibitor complex. These observations could be potentially utilized for the rational design and optimization of novel (structurally similar, with phthalimide moiety, or different) noncompetitive DPP-4 inhibitors, which are anyway rare, but favorable in terms of the saturation of substrate competition.