The cytochrome bc1complex(the bc1complex or complex Ⅲ) is an attractive target for the discovery of numerous pharmaceuticals and pesticides. In order to identify new lead structures for this target, a new series of m...The cytochrome bc1complex(the bc1complex or complex Ⅲ) is an attractive target for the discovery of numerous pharmaceuticals and pesticides. In order to identify new lead structures for this target, a new series of molecules, N-(4-aryloxyphenyl)phthalimides, were designed and synthesized in a straightforward manner. Our design strategy was to introduce a 4-aryloxyphenyl group, a fragment which exhibited promising bc1complex-inhibiting properties, into the aryl group of the valuable N-arylphthalimide backbone. Afterward, the biochemical evaluation of the newly synthesized compounds was carried out,and the results implied that several compounds demonstrated good activities against succinatecytochrome reductase(SCR, a mixture of mitochondrial complex Ⅱ and the bc1complex). Further studies confirmed that 3e’, a representative compound in this paper, was identified as an inhibitor of the bc1complex. Furthermore, computational simulations were also performed to better understand binding of 3e’ to the enzyme complex, which indicated that 3e’ should bind to the Qosite of the bc1complex.Consequently, we harbor the idea that this paper can provide a solid platform for synthesis and discovery of other bc1complex inhibitors.展开更多
An adenine nucleotide derivative 2-aminoadenosine 5＇-triphosphate was chemically synthesized through four steps and was characterized with 1H NMR, 31p NMR, 13C NMR, EA and FT-IR. Its ultraviolet and fluorescence prop...An adenine nucleotide derivative 2-aminoadenosine 5＇-triphosphate was chemically synthesized through four steps and was characterized with 1H NMR, 31p NMR, 13C NMR, EA and FT-IR. Its ultraviolet and fluorescence properties at various pH values were studied. Two pKa values for the compound were determined by the curves of UV absorption dependency on pH, Which were 0.68 and 4.83, respectively. The values were consistent with those calculated from ACD/Labs software. In addition, hydrolysis of the adenine nucleotide derivative in the catalysis of potato apyrase was studied. The competition of the ATP analogue with ATP for potato apyrase＇ active site was proved to be a sequential reaction mechanism.展开更多
In current study toxicological profile of a commonly used herbal formulation was evaluated that is used extensively for gynecological disorders like menorrhagia, metrorrhagia, leucorrhea, irregular menstrual cycle, pr...In current study toxicological profile of a commonly used herbal formulation was evaluated that is used extensively for gynecological disorders like menorrhagia, metrorrhagia, leucorrhea, irregular menstrual cycle, pre-menstrual syndrome and post-menopausal bleeding. It was also claimed to strengthen endometrium and ovaries. Since this herbal formulation was been used by a large number of population hence there was a need to assess acute and sub-chronic toxicity. Acute oral toxicity (LD50) was observed in albino mice using standard protocols whereas sub-chronic, hematological and histopathological studies were assessed on 24 albino rabbits after giving herbal formulation for 60 days in two doses (20 and 60 mg/kg) against control groups. The outcomes of present study showed that the drug is safe up to 5000 mg/kg following acute oral toxicity test and no mortality was observed during sub chronic toxicity studies. Results of sub-chronic toxicity did not show any significant changes in biochemical, hematological and histopathological parameters. However, some indicators such as urea, creatinine, hemoglobin, and RBC count were altered, but these changes do not correlate with the histopathological results and may be associated to intra individual variations. Despite the safety of the drug in few animals, clinical trials and more investigations on a large number of animals are essentially needed to establish safety and efficacy of the herbal formulation.展开更多
基金supported by the National Natural Science Foundation of China(Nos.21502062,21272091 and 21472063)Hubei Provincial Department of Education(No.Q20102606)+3 种基金Xiangyang Science and Technology Bureau(No.2010GG1B33)Structural Biomedicine and Pharmacochemistry of Hubei University of Arts and Sciencethe support from the Russian Foundation for Basic Research(No.18-29-04047)the Tomsk Polytechnic University Competitiveness Enhancement Program grant(No.VIU-195/2018)
文摘The cytochrome bc1complex(the bc1complex or complex Ⅲ) is an attractive target for the discovery of numerous pharmaceuticals and pesticides. In order to identify new lead structures for this target, a new series of molecules, N-(4-aryloxyphenyl)phthalimides, were designed and synthesized in a straightforward manner. Our design strategy was to introduce a 4-aryloxyphenyl group, a fragment which exhibited promising bc1complex-inhibiting properties, into the aryl group of the valuable N-arylphthalimide backbone. Afterward, the biochemical evaluation of the newly synthesized compounds was carried out,and the results implied that several compounds demonstrated good activities against succinatecytochrome reductase(SCR, a mixture of mitochondrial complex Ⅱ and the bc1complex). Further studies confirmed that 3e’, a representative compound in this paper, was identified as an inhibitor of the bc1complex. Furthermore, computational simulations were also performed to better understand binding of 3e’ to the enzyme complex, which indicated that 3e’ should bind to the Qosite of the bc1complex.Consequently, we harbor the idea that this paper can provide a solid platform for synthesis and discovery of other bc1complex inhibitors.
文摘An adenine nucleotide derivative 2-aminoadenosine 5＇-triphosphate was chemically synthesized through four steps and was characterized with 1H NMR, 31p NMR, 13C NMR, EA and FT-IR. Its ultraviolet and fluorescence properties at various pH values were studied. Two pKa values for the compound were determined by the curves of UV absorption dependency on pH, Which were 0.68 and 4.83, respectively. The values were consistent with those calculated from ACD/Labs software. In addition, hydrolysis of the adenine nucleotide derivative in the catalysis of potato apyrase was studied. The competition of the ATP analogue with ATP for potato apyrase＇ active site was proved to be a sequential reaction mechanism.
文摘In current study toxicological profile of a commonly used herbal formulation was evaluated that is used extensively for gynecological disorders like menorrhagia, metrorrhagia, leucorrhea, irregular menstrual cycle, pre-menstrual syndrome and post-menopausal bleeding. It was also claimed to strengthen endometrium and ovaries. Since this herbal formulation was been used by a large number of population hence there was a need to assess acute and sub-chronic toxicity. Acute oral toxicity (LD50) was observed in albino mice using standard protocols whereas sub-chronic, hematological and histopathological studies were assessed on 24 albino rabbits after giving herbal formulation for 60 days in two doses (20 and 60 mg/kg) against control groups. The outcomes of present study showed that the drug is safe up to 5000 mg/kg following acute oral toxicity test and no mortality was observed during sub chronic toxicity studies. Results of sub-chronic toxicity did not show any significant changes in biochemical, hematological and histopathological parameters. However, some indicators such as urea, creatinine, hemoglobin, and RBC count were altered, but these changes do not correlate with the histopathological results and may be associated to intra individual variations. Despite the safety of the drug in few animals, clinical trials and more investigations on a large number of animals are essentially needed to establish safety and efficacy of the herbal formulation.
