Abstract:Cancer is one of the leading causes of death worldwide. With the increase in life expectancy, the number of cancer cases has reached unprecedented levels. In this scenario, the pharmaceutical industry has made significant investments in this therapeutic area. Despite these efforts, cancer drug research remains a remarkably challenging field, and therapeutic innovations have not yet achieved expected clinical results. However, the physiopathology of the disease is now better understood, and the discovery of nov… Show more
“…Since cancer incidence keeps rising each year [1,2], the scientific community and pharmaceutical industry have focused their attention on the discovery of new drugs or drug adjuvants to improve the fight against this disease [3]. Consequently, one hotspot of interest for drug discovery is anticancer drugs, whose rising costs have been applied to drug research and development [3,4].…”
Preussin, a hydroxyl pyrrolidine derivative isolated from the marine sponge-associated fungus Aspergillus candidus KUFA 0062, displayed anticancer effects in some cancer cell lines, including MCF7. Preussin was investigated for its cytotoxic and antiproliferative effects in breast cancer cell lines (MCF7, SKBR3, and MDA-MB-231), representatives of major breast cancers subtypes, and in a non-tumor cell line (MCF12A). Preussin was first tested in 2D (monolayer), and then in 3D (multicellular aggregates), cultures, using a multi-endpoint approach for cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), resazurin and lactate dehydrogenase (LDH)) and proliferative (5-bromo-2′-deoxyuridine (BrdU)) assays, as well as the analysis of cell morphology by optical/electron microscopy and immunocytochemistry for caspase-3 and ki67. Preussin affected cell viability and proliferation in 2D and 3D cultures in all cell lines tested. The results in the 3D culture showed the same tendency as in the 2D culture, however, cells in the 3D culture were less responsive. The effects were observed at different concentrations of preussin, depending on the cell line and assay method. Morphological study of preussin-exposed cells revealed cell death, which was confirmed by caspase-3 immunostaining. In view of the data, we recommend a multi-endpoint approach, including histological evaluation, in future assays with the tested 3D models. Our data showed cytotoxic and antiproliferative activities of preussin in breast cancer cell lines in 2D and 3D cultures, warranting further studies for its anticancer potential.
“…Since cancer incidence keeps rising each year [1,2], the scientific community and pharmaceutical industry have focused their attention on the discovery of new drugs or drug adjuvants to improve the fight against this disease [3]. Consequently, one hotspot of interest for drug discovery is anticancer drugs, whose rising costs have been applied to drug research and development [3,4].…”
Preussin, a hydroxyl pyrrolidine derivative isolated from the marine sponge-associated fungus Aspergillus candidus KUFA 0062, displayed anticancer effects in some cancer cell lines, including MCF7. Preussin was investigated for its cytotoxic and antiproliferative effects in breast cancer cell lines (MCF7, SKBR3, and MDA-MB-231), representatives of major breast cancers subtypes, and in a non-tumor cell line (MCF12A). Preussin was first tested in 2D (monolayer), and then in 3D (multicellular aggregates), cultures, using a multi-endpoint approach for cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), resazurin and lactate dehydrogenase (LDH)) and proliferative (5-bromo-2′-deoxyuridine (BrdU)) assays, as well as the analysis of cell morphology by optical/electron microscopy and immunocytochemistry for caspase-3 and ki67. Preussin affected cell viability and proliferation in 2D and 3D cultures in all cell lines tested. The results in the 3D culture showed the same tendency as in the 2D culture, however, cells in the 3D culture were less responsive. The effects were observed at different concentrations of preussin, depending on the cell line and assay method. Morphological study of preussin-exposed cells revealed cell death, which was confirmed by caspase-3 immunostaining. In view of the data, we recommend a multi-endpoint approach, including histological evaluation, in future assays with the tested 3D models. Our data showed cytotoxic and antiproliferative activities of preussin in breast cancer cell lines in 2D and 3D cultures, warranting further studies for its anticancer potential.
“…It is hypothesized that Cu(I) complexes had efficient uptake through lipid cell membrane than Cu(II) derivatives [20]. Therefore, the structure-activity relationship (SAR) analysis disclosed that cytotoxic profile of the Cu(I) compounds is dependent on the lipophilic property of the fluoroquinolone ligand [21].…”
Platinum-based metallodrugs candidates are extensively evaluated as antineoplastic agents against several tumoral cell lines, representing a considerable advance in cancer treatment. On the other hand, the hostile off-site toxicity has been limited their potential uses in clinical step. Thus, the search for novel active and selective antitumor drugs is a leading issue in the medicinal inorganic chemistry. As follow, the research focused on less toxic metals has strategic importance and several copper complexes have revealed promising activity. In addition, copper is an essential metal, which can increase the chances of reduced side effects. This review brings some copper complexes that showed highlighted anticancer activity as drug prototypes from the last ten years (2010-2019), involving phosphine and isatin ligands, different redox states, modes of action and the study of structure-activity relationship (SAR).
“…Одним из перспективных направлений является получение терапевтических МКА к возбудителям вирусных и бактериальных инфекций. Препараты на основе МКА успешно применяются при лечении некоторых видов рака (рак толстого кишечника, немелкоклеточный рак легких, глиобластома, метастазирующий рак почки) и аутоиммунных заболеваний (ревматоидный артрит, псориаз, болезнь Крона), а также для подавления иммунной системы после трансплантации органов [14].…”
Резюме. Инфекционные заболевания вирусной этиологии являются одной из важнейших проблем здравоохранения. В России ежегодно регистрируется около 50 млн случаев инфекционных заболеваний, до 90% из которых приходится на долю острых респираторных вирусных инфекций. В неэпидемические по гриппу сезоны в качестве основных возбудителей ОРВИ выступают аденовирусы, респираторно-синцитиальный вирус, вирусы парагриппа и др. Инфекционные заболевания, вызванные аденовирусами, характеризуется полиморфизмом проявлений, что делает их интересными для изучения и в то же время сложными для клинической диагностики. Применение быстрых, чувствительных и специфичных тестов является актуальным для рутинной клинической лабораторной практики. Для дифференциальной диагностики аденовирусных инфекций в России широко применяются иммуноферментный и иммунофлуоресцентный анализ с применением поликлональных специфичных сывороток, характер и спектр реагирования которых зависит от особенностей иммунного ответа животного-продуцента и состава вырабатываемых антител. Включение в состав современных иммунологических тестов моноклональных антител, направленных к определенным антигенным детерминантам в составе вируса, определяет высокую чувствительность, специфичность и необходимый уровень стандартизации препаратов. Гексон аденовирусов содержит родоспецифические антигены и обладает достаточно консервативной аминокислотной последовательностью среди аденовирусов разных типов. Кроме того, этот белок синтезируется в инфицированных клетках в больших количествах и может быть получен в нативной форме, что определило его использование в качестве иммуногена для получения моноклональных антител, способных выявлять аденовирусы различных типов. Получена панель моноклональных антител к гексону аденовируса. Изучены их биологические и диагностические свойства. По результатам вестерн блоттинга можно заключить, что все моноклональные антитела связываются с олигомерами гексона в составе аденовируса. Специфическая активность новых моноклональных антител в отношении аденовирусов разных типов исследована методами иммуноферментного и непрямого иммунофлуоресцентного анализа. Наибольшей специфической активностью в иммуноферментном анализе обладают моноклональные антитела 4B7 и 6B12, титр антител составил 10-6. Наибольшей активностью в отношении различных типов аденовирусов в непрямом иммунофлуоресцентном анализе обладали моноклональные антитела 6В12, при использовании которых в инфицированных аденовирусами 3, 4, 6 и 19 типов клетках наблюдалась яркая гранулярная флуоресценция Адрес для переписки:
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