Публикации

Inhibition of oxidative phosphorylation by semisynthetic oligomycins in rat liver mitochondria / O. Omelchuk, S. Nesterov, L. Lysenkova et al. // FEBS open bio. — 2019. — Vol. 9, no. S1. — P. 138. [ DOI ]

New anthra[2,3-b]furancarboxamides: A role of positioning of the carboxamide moiety in antitumor properties / Y. Volodina, L. Dezhenkova, A. Tikhomirov et al. // European Journal of Medicinal Chemistry. — 2019. — no. 165. — P. 31–45. Derivatives of the anthraquinone (anthracene-9,10-dione) such as doxorubicin, mitoxantrone and others have proved great clinical efficacy for decades. Currently the search in this exceptionally productive chemical class is aimed at optimization of antitumor properties including circumvention of drug resistance. Previously we have reported that heteroarene-fused anthraquinones fused to a 5-membered heterocyclic ring are advantageous in killing drug resistant tumor cells. Herein we present the synthesis and antitumor properties of a series of new anthra[2,3-b]furan-2-carboxamides. Vast majority of new derivatives were similarly cytotoxic to wild type tumor cell lines and their isogenic sublines with P-glycoprotein overexpression and/or p53 inactivation. Comparison of structurally close derivatives varying in their position relative to the furan moiety, that is, furan-3-carboxamide 1vs furan-2-carboxamides 5 and 6, revealed fundamental differences in the cytotoxicity profiles, formation of drug-DNA complexes, efficacy of topoisomerase 1 inhibition and mechanisms of tumor cell death. Together with previous SAR data on the role of individual substituents, these results provide evidence that regioisomerization of anthra[2,3-b]furancarboxamides generates the practically perspective derivatives whose properties may vary significantly. [ DOI ]

Synthesis, antimicrobial and antiproliferative properties of epi-oligomycin a, the (33s)-diastereomer of oligomycin a / L. N. Lysenkova, O. Y. Saveljev, O. A. Omelchuk et al. // Natural Product Research. — 2019. [ DOI ]

Atp-synthase inhibition by semi-synthetic oligomycin a derivatives / O. A. Omelchuk, D. A. Mavletova, T. A. Koshenko et al. // FEBS open bio. — 2018. — Vol. 8, no. S1. — P. 487–487. [ DOI ]

Tikhomirov A. S., Shtil A. A., Shchekotikhin A. E. Advances in the discovery of anthraquinone-based anticancer agents // Recent Patents on Anti-Cancer Drug Discovery. — 2018. — Vol. 13, no. 2. Background: The anthracene-9,10-dione (anthraquinone) derivatives represent an exceptionally valuable class in anticancer drug development. An outstanding antitumor potency of the anthracycline antibiotics attracted the attention of medicinal chemists since the discovery of these chemotypes. The prominent anthraquinone-based drugs doxorubicin, mitoxantrone as well as more recent epirubicin, idarubicin, and valrubicin are successfully used in chemotherapy of hematological malignancies and solid tumors. The anthraquinone core remains a promising scaffold for the search of new optimized drug candidates. Objective: In this study, we analyze the progress in discovery and development of antitumor anthracene- 9,10-diones based on patent and journal publications in 2008-2017. The main goal is to dissect novel chemotypes of anthraquinone derivatives; other important issues such as the success in bioconjugate chemistry of anthraquinone containing agents as well as the patents on new applications of anthracyclines are beyond the scope of this review. Conclusion: A number of newly discovered natural products, the perspective directions for chemical modifications to optimize the anticancer properties, and novel intracellular targets demonstrate that anthracene- 9,10-diones deserve further in-depth investigation as an important source of drug candidates. [ DOI ]

Aminomethylation of heliomycin: Preparation and anticancer characterization of the first series of semi-synthetic derivatives / G. Y. Nadysev, A. S. Tikhomirov, M.-H. Lin et al. // European Journal of Medicinal Chemistry. — 2018. — Vol. 143. — P. 1553–1562. Abstract A series of 4-aminomethyl derivatives of heliomycin 1 was prepared using the Mannich reaction. The modification significantly improved aqueous solubility of the initially poorly soluble antibiotic. Testing the antiproliferative efficacy revealed a potent activity of heliomycin as well as its new derivatives on a panel of mammalian tumor cells including drug resistant variants. In contrast to 1 the new derivatives 7a, 7l, 7p generated a high level of ROS associated with induction of apoptosis in T24 bladder cancer cells. Introduction of 4-aminomethyl moiety increased the affinity to DNA and the ability to inhibit topoisomerase 1 making 7p the most promising candidate for further preclinical evaluation. Thus, aminomethylation is the first-in-class successful transformation of the antibiotic 1 resulting in an improved water solubility of derivatives and promising properties in search of novel anticancer drug candidates. [ DOI ]

Heterocyclic analogs of 5,12-naphthacenequinone 15*. synthesis of new anthra[2,3-b]thiophene-3(2)-carboxylic acids / D. V. Andreeva, Y. B. Sinkevich, A. S. Tikhomirov et al. // Chemistry of Heterocyclic Compounds. — 2018. — Vol. 54, no. 6. — P. 612–617. [ DOI ]

New antitumor anthra[2,3-b]furan-3-carboxamides: Synthesis and structure-activity relationship / A. S. Tikhomirov, L. Chia-Yang, Y. L. Volodina et al. // European Journal of Medicinal Chemistry. — 2018. — Vol. 148. — P. 128–139. Chemical modifications of the anthraquinone scaffold are aimed at optimization of this exceptionally productive class of antitumor drugs. In particular, our previously reported anthra[2,3-b]furan-3- carboxamides demonstrated a high cytotoxic potency in cell culture and in vivo. In this study, we expanded our series of anthra[2,3-b]furan-3-carboxamides by modifying the key functional groups and dissected the structure-activity relationship within this chemotype. The majority of new compounds inhibited the growth of mammalian tumor cell lines at submicromolar to low micromolar concentrations. We found that 4,11-hydroxy groups as well as the carbonyl moiety in the carboxamide fragment were critical for cytotoxicity whereas the substituent at the 2-position of anthra[2,3-b]furan was not. Importantly, the new derivatives were similarly potent against wild type cells and their variants resistant to doxorubicin due to P-glycoprotein (Pgp) expression or p53 inactivation. The most cytotoxic derivatives 6 and 9 attenuated plasmid DNA relaxation by topoisomerase 1. Finally, we demonstrated that 6 and 9 at 1 mM induced intracellular oxidative stress, accumulation in G2/M phase of the cell cycle, and apoptosis in gastric carcinoma cell lines regardless of their p53 status. These results further substantiate the potential of anthra[2,3-b]furan-3-carboxamides as antitumor drug candidates. [ DOI ]

Novel quinoxaline-2-carbonitrile-1,4-dioxide derivatives suppress hif1α activity and circumvent mdr in cancer cells / A. M. Scherbakov, A. M. Borunov, G. I. Buravchenko et al. // Cancer Investigation. — 2018. — no. 0. — P. 1–11. A series of 3-aryl/hetarylquinoxaline-2-carbonitrile-1,4-dioxides was synthesized and evaluated against breast cancer cell lines in normoxia and hypoxia. Selected compounds in this series demonstrated better cytotoxicity and comparable hypoxia selectivity than tirapazamine. In contrast to Dox, quinoxaline-1,4-dioxides showed potent cytotoxicity against different MDR cells. Compound 2g inhibits of cancer cell growth through p53-independent mechanisms. Our results showed that compound 2g sensitized MCF-7 cells to metformin in hypoxia. Treatment with 2g results in the increase of ROS accumulation in cancer cells. Compound 2g can be considered as the lead compound for further anticancer drug design, evaluation, and development of new potent antitumor agents. KEYWORDS: Antiproliferative activity, drug resistance, HIF1α activity suppression, hypoxia, quinoxaline-2-carbonitrile-1,4-dioxide. [ DOI ]

Omelchuk O. A., Tevyashova A. N., Shchekotikhin A. E. Recent advances in antifungal drug discovery based on polyene macrolide antibiotics // Russian Chemical Reviews. — 2018. — Vol. 87, no. 12. — P. 1206–1225. [ DOI ]

Synthesis and biological activity of 16,33-o,o-diformyl-16,17-dihydro-16(s),17(r)-dihydroxyoligomycin a and 33-o-formyloligomycin a / O. A. Omelchuk, N. M. Belov, V. B. Tsvetkov et al. // Макрогетероциклы. — 2018. — Vol. 11, no. 2. — P. 181–192. [ DOI ]

Synthesis and biological activity of 7(7,11)-hydroderivatives of oligomycin a / O. A. Omelchuk, L. N. Lysenkova, N. M. Belov et al. // Макрогетероциклы. — 2018. — Vol. 11, no. 3. — P. 322–328. [ DOI ]

Новые противогрибковые производные олигомицина А / О. А. Омельчук, Л. Н. Лысенкова, Н. Э. Грамматикова, А. Е. Щекотихин // Успехи медицинской микологии. — 2018. — Т. 8. — С. 178–178.

Современные тенденции органической химии в университетах России / А. И. Коновалов, И. С. Антипин, В. А. Бурилов и др. // Журнал органической химии. — 2018. — Т. 54, № 2. — С. 161–360.

1,4-Диоксиды 3-арилхиноксалин-2-карбонитрилов: роль заместителей в гипоксической цитотоксичности. Успехи молекулярной онкологии / А. М. Борунов, Г. И. Буравченко, О. Е. Андреева и др. // Успехи молекулярной онкологии. — 2017. — Т. 4. — С. 88–89.

Development and pharmaceutical evaluation of the anticancer anthrafuran/cavitron complex, a prototypic parenteral drug formulation / H. M. Treshalina, V. I. Romanenko, D. N. Kaluzhny et al. // European Journal of Pharmaceutical Sciences. — 2017. — Vol. 109. — P. 631–637. [ DOI ]

Heterocyclic analogs of 5,12-naphthacenequinone 14. synthesis of naphtho[2,3-f]indole-3-carboxylic acid derivatives / A. S. Tikhomirov, V. A. Litvinova, Y. N. Luzikov et al. // Chemistry of Heterocyclic Compounds. — 2017. — Vol. 53, no. 10. — P. 1072–1079. [ DOI ]

Organic chemistry. history and mutual relations of universities of russia / I. S. Antipin, M. A. Kazymova, M. A. Kuznetsov et al. // Russian Journal of Organic Chemistry. — 2017. — Vol. 53, no. 9. — P. 1275–1437. [ DOI ]

Rna g-quadruplexes in kirsten ras (kras) oncogene as targets for small molecules inhibiting translation / M. Giulia, C. Susanna, M. Jessica et al. // Journal of Medicinal Chemistry. — 2017. [ DOI ]

Searching for new oligomycin a derivatives with improved selectivity against malignant cells / O. A. Omelchuk, V. B. Tsvetkov, L. G. Dezhenkova et al. // FEBS Journal. — 2017. — Vol. 284. — P. P.5.2–042. [ DOI ]

Verification of oligomycin a structure: synthesis and biological evaluation of 33-dehydrooligomycin a / L. N. Lysenkova, O. Y. Saveljev, N. E. Grammatikova et al. // Journal of Antibiotics. — 2017. — Vol. 70. — P. 871–877. Although, the structure of oligomycin A (1) was confirmed by spectroscopic and chemical evaluations, some crystallographic data cast doubt on the originally adopted structure of the side 2-hydroxypropyl moiety of this antibiotic. It was suggested that the side chain of the oligomycin is enol-related (2-hydroxy-1-propenyl). To clarify this matter we synthesized and evaluated 33-dehydrooligomycin A (2) prepared by the Kornblum oxidation of 33-O-mesyloligomycin A (3) by dimethyl sulfoxide. NMR data for 33-dehydrooligomycin (2) and results of quantum chemical calculations have shown that this derivative exists in the keto rather than in the enol tautomer 2a. The in vitro antimicrobial activity of 2 was approximately two times weaker in comparison with oligomycin A against Streptomyces fradiae ATCC-19609 and reference Candida spp. strains and similar activity against certain filamentous fungi. The docking binding estimate of 2 with FOF1ATP synthase showed a slight decrease in binding affinity for 2 when compared with oligomycin A; that correlated with its activity against S. fradiae ATCC 19609 that is supersensitive to oligomycin A. The in vitro antiproliferative activities of 2 are also discussed. [ DOI ]

Новые производные антрафурана: химическая структура и механизмы цитотоксичности / Ю. Л. Володина, А. С. Тихомиров, Л. Г. Деженкова и др. // Российский биотерапевтический журнал. — 2017. — Т. 16. — С. 20–21.

ОРГАНИЧЕСКАЯ ХИМИЯ. ИСТОРИЯ И ВЗАИМНАЯ СВЯЗЬ УНИВЕРСИТЕТОВ РОССИИ / И. С. Антипин, М. А. Казымова, М. А. Кузнецов и др. // Журнал органической химии. — 2017. — Т. 53, № 9. — С. 1257–1408.

Поиск производных олигомицина, селективно ингибирующих опухолевый рост / О. А. Омельчук, Л. Н. Лысенкова, Л. Г. Деженкова, А. Е. Щекотихин // Российский биотерапевтический журнал. — 2017. — Т. 16. — С. 59.

Цитотоксическая активность 7-аминопроизводных 1,4-диоксида 3-фенил-2-хиноксалинкарбонитрила / Г. И. Буравченко, Ю. А. Блинова, Н. Э. Вавилов и др. // Российский биотерапевтический журнал. — 2017. — Т. 16, № 16.

Discovery of antitumor anthra[2,3-b]furan-3-carboxamides: Optimization of synthesis and evaluation of antitumor properties / A. E. Shchekotikhin, L. G. Dezhenkova, V. B. Tsvetkov et al. // European Journal of Medicinal Chemistry. — 2016. — Vol. 112. — P. 114–129. Anthraquinones and their analogues, in particular heteroarene-fused anthracendiones, are prospective scaffolds for new compounds with improved antitumor characteristics. We herein report the use of a ‘scaffold hopping’ approach for the replacement of the core structure in the previously discovered hit compound naphtho[2,3-f]indole-5,10-dione 2 with an alternative anthra[2,3-b]furan-5,10-dione scaffold. Among 13 newly synthesized derivatives the majority of 4,11-dihydroxy-2-methyl-5,10-dioxoanthra[2,3-b]furan-3-carboxamides demonstrated a high antiproliferative potency against a panel of wild type and drug resistant tumor cell lines, a property superior over the reference drug doxorubicin or lead naphtho[2,3-f]indole-5,10-dione 2. At lowmicromolar concentrations the selected derivative of (R)-3-aminopyrrolidine 3c and its stereoisomer (S)-3-aminopyrrolidine 3d caused an apoptotic cell death preceded by an arrest in the G2/M phase. Studies of intracellular targets showed that 3c and 3d formed stable intercalative complexes with the duplex DNA as determined by spectral analysis and molecular docking. Both 3c and 3d attenuated topoisomerase 1 and 2 mediated unwinding of the supercoiled DNA via a mechanism different from conventional DNA-enzyme tertiary complex formation. Furthermore, 3d decreased the activity of selected human protein kinases in vitro, indicating multiple targeting by the new chemotype. Finally, 3d demonstrated an antitumor activity in a model of murine intraperitoneally transplanted P388 leukemia, achieving the increase of animal life span up to 262% at tolerable doses. Altogether, the ‘scaffold hopping’ demonstrated its productivity for obtaining new perspective antitumor drug candidates. [ DOI ]

Heterocyclic analogs of 5,12-naphtacenequinone 13*. synthesis of 4,11-diaminoanthra[2,3-b]furan-5,10-diones and sulfur-containing analogs / A. S. Tikhomirov, E. E. Bykov, Y. N. Luzikov et al. // Chemistry of Heterocyclic Compounds. — 2016. — Vol. 52, no. 10. — P. 797–802. [ DOI ]

ВЛИЯНИЕ ЗАМЕСТИТЕЛЕЙ В ПЕРИ-ПОЛОЖЕНИЯХ НА АНТИПРОЛИФЕРАТИВНЫЕ СВОЙСТВА АНТРАФУРАНКАРБОКСАМИДОВ / О. А. Омельчук, А. С. Тихомиров, Л. Г. Деженкова, А. Е. Щекотихин // Российский биотерапевтический журнал. — 2016. — Т. 15. — С. 81–81.

Омельчук О. А., Тихомиров А. С., Щекотихин А. Е. МЕТОДЫ АННЕЛИРОВАНИЯ ФУРАНОВОГО ЯДРА К АРЕНАМ // Успехи химии. — 2016. — Т. 85, № 8. — С. 817–835. Благодаря уникальным физико-химическим, химическим и биологическим свойствам бензо[ b ]фураны нашли применение в различных областях химии и технологии. Прежде всего следует отметить широкий спектр биологической активности природных и синтетических производных бензо[ b ]фурана, а также его конденсированных аналогов (нафтофуранов, антрафуранов и др.), который обусловливает значительный интерес ученых к использованию этих гетероциклов в качестве важных "строительных блоков" при создании лекарственных препаратов. В обзоре рассмотрены способы аннелирования фуранового ядра к аренам, разработанные преимущественно за последнее десятилетие. Проанализированы тенденции развития методов синтеза бензо[ b ]фуранов, ряд из которых показал высокую эффективность при получении полифункциональных производных. Библиография - 110 ссылок. [ DOI ]

Производные антрафуранкарбоксамидов с преимущественной цитотоксичностью для клеток миелоидного лейкоза / Л. Г. Деженкова, Ю. Л. Володина, А. С. Тихомиров и др. // Гематология и трансфузиология. — 2016. — Т. 61, № 1. — С. 111–111.

СЕКВЕНИРОВАНИЕ И АНАЛИЗ РЕЗИСТОМА / А. А. Ватлин, О. Б. Беккер, Л. Н. Лысенкова и др. // Генетика. — 2016. — Т. 52. — С. 723–728.

Синтез 33-(r,s)-бромо-33-дезоксиолигомицина А / Л. Н. Лысенкова, О. Ю. Савельев, А. М. Королев и др. // Макрогетероциклы. — 2016. — Т. 9, № 3. — С. 307–313. В статье представлен синтез, физико-химические свойства и антимикробная активность 33-бромо-33-дезоксиолигомицина А (3), полусинтетического производного олигомицина А (1). Бромоолигомицин А(3) получен в виде смеси двух 33-(R,S)-диастереомеров из 33-О-мезилолигомицина А (2) замещением мезилоксигруппы при действии тетрабутиламмоний бромида или бромида калия в присутствии межфазного катализатора. [ DOI ]

Синтез и биологические свойства 2,3,16,17,18,19-гексагидроолигомицина А / О. А. Омельчук, Н. М. Белов, В. Б. Цветков и др. // Макрогетероциклы. — 2016. — Т. 9, № 4. — С. 453–461. В статье описан синтез производного олигомицина А (1) – 2,3,16,17,18,19-гексагидроолигомицина А (3), а также его физико-химические, спектральные и биологические свойства. Гидрирование на Pd/C олигомицина А (1) в мягких условиях приводит к продукту восстановления трех двойных С=С связей. Структура пергидроолигомицина (3) доказана методами ЯМР-спектроскопии и масс-спектрометрии высокого разрешения. Исследованы противогрибковые, антиактиномикозные и антипролиферативные свойства нового антибиотика 3. Выявлена селективная активность пергидроолигомицина (3) в отношении ряда штаммов грибов рода Candida, тогда как активность для других тест-культур была в 3–20 раз ниже активности исходного олигомицина А. Методами компьютерного моделирования проведено сравнительное исследование комплексообразования при взаимодействии антибиотиков с мишенью – F0-субъединицей АТФ-синтазы, результаты которого согласуются с результатами биологического скрининга. [ DOI ]

Химическое модулирование действия олигомицина А, направленное на возбудителей кандидоза / О. А. Омельчук, Л. Н. Лысенкова, Н. Э. Грамматикова, А. Е. Щекотихин // Современная микология в России. — 2016. — Т. 7. — С. 254.

Тихомиров А. С., Деженкова Л. Г., Щекотихин А. Е. Цитотоксические свойства антрафуранкарбоксамидов, содержащих cf3-группу в положении 2 // Российский биотерапевтический журнал (Russian Journal of Biotherapy),. — 2016. — № 1. — С. 108–108.

Potent apoptotic response induced by chloroacetamidine anthrathiophenediones in bladder cancer cells / S. Cogoi, L. E. Xodo, S. Zorzet, A. E. Shchekotikhin // Journal of Medicinal Chemistry. — 2015. — Vol. 58. — P. 5476–5485.

Synthesis and anti-actinomycotic activity of the oligomycin a thiocyanato derivative modified at 2-oxypropyl side chain / L. N. Lysenkova, I. A. Godovikov, A. M. Korolev et al. // Макрогетероциклы. — 2015. — Vol. 8. — P. 424–428. A novel way of chemical modification of the antibiotic oligomycin A at the 2-oxypropyl side chain was developed. Previously obtained 33-O-mesyl oligomycin A was used at the reaction with the potassium thiocyanate to produce (33S)-33-deoxy-33-thiocyanatooligomycin in 66 % yield. (33S)-33-Deoxy-33-thiocyanatooligomycin A has demonstrated a lower potency active against S. fradiae and S. albus than oligomycin A. [ DOI ]

Synthesis and characterization of 4,11-diaminoanthra[2,3‑b]furan- 5,10-diones: Tumor cell apoptosis through tnox-modulated nad+/ nadh ratio and sirt1 / A. S. Tikhomirov, A. E. Shchekotikhin, L. Yi-Hui et al. // Journal of Medicinal Chemistry. — 2015. — Vol. 58. — P. 9522–9534. A series of new 4,11-diaminoanthra[2,3-b]furan-5,10-dione derivatives with different side chains were synthesized.Selected 2-unsubstituted derivatives 11−14 showed high antiproliferative potency on a panel of mammalian tumor cell lines including multidrug resistance variants. Compounds 11−14 utilized multiple mechanisms of cytotoxicity including inhibition of Top1/Top2-mediated DNA relaxation, reduced NAD+/NADH ratio through tNOX inhibition, suppression of a NAD+- dependent sirtuin 1 (SIRT1) deacetylase activity, and activation of caspase-mediated apoptosis. Here, for the first time, we report that tumor-associated NADH oxidase (tNOX) and SIRT1 are important cellular targets of antitumor anthracene-9,10-diones. [ DOI ]

Щекотихин А. Е. ПРОТИВООПУХОЛЕВЫЕ ЛИГАНДЫ НА ОСНОВЕ АНТРАТИОФЕНДИОНОВ:МОДУЛИРОВАНИЕ БИОЛОГИЧЕСКИХ СВОЙСТВ ПУТЕМ МОДИФИКАЦИИ СТРУКТУРЫ БОКОВЫХ ЦЕПЕЙ // Успехи молекулярной онкологии. — 2015. — Т. 2. — С. 18–19.

Cogoi S., Xodo L. E., Shchekotikhin A. E. Hras is silenced by two neighboring g-quadruplexes and activated by maz, a zinc-finger transcription factor with dna unfolding property // Nucleic Acids Research. — 2014. — Vol. 42. — P. 8379–8388.

Novel multi-targeting anthra[2,3-b]thiophene-5,10-diones with guanidine-containing side chains: Interaction with telomeric g-quadruplex, inhibition of telomerase and topoisomerase i and cytotoxic properties / N. Ilyinsky, A. Shchyolkina, O. Borisova et al. // European Journal of Medicinal Chemistry. — 2014. — Vol. 85. — P. 605–614. Novel generations of antitumor anthraquinones are expected to be advantageous over the conventional chemotherapeutic agents. Previous structure-activity relationship studies demonstrated an importance of the positively charged side chains conjugated to anthra[2,3-b]thiophene-5,10-dione scaffolds. Exploring a role of individual side chain moieties in binding to the duplex and G-quadruplex DNA, modulation of telomerase and topoisomerase I activities, intracellular accumulation and cytostatic potency, we herein analyzed a series of reported and newly synthesized guanidine-containing derivatives of anthra[2,3-b]thiophene-5,10-dione. We found that the number of cationic side chains (namely, two) is critical for a tight interaction with human telomeric G-quadruplex (TelQ). Along with a larger drug-TelQ association constant, the telomerase attenuation by anthrathiophenediones with two basic groups in the side chains was more pronounced than by the analogs bearing one basic group. For mono-guanidinated compounds the substituent with the amino group in the side chain provided better TelQ affinity than the methylamine residue. The intracellular uptake of the mono-guanidino derivative with two side chains was >2-fold higher than the respective value for the bis(guanidino) derivative. This difference can explain a lower antiproliferative potency of bis(guanidine) containing compounds. Thus, the modifications of side chains of anthra[2,3-b]thiophene-5,10-dione differently modulated drug-target interactions and cellular effects. Nevertheless, the selected compound 11-(3-aminopropylamino)-4-(2-guanidinoethylamino)anthra[2,3-b]thiophene-5,10-dione 13 demonstrated a high affinity to TelQ and the ability to stabilize the quadruplex structure. These properties were paralleled by reasonable potency of 13 as a telomerase/topoisomerase I inhibitor and an antiproliferative agent. These results indicate that the structural elements of anthra[2,3-b]thiophene-5,10-dione derivatives can be balanced to yield a candidate for further preclinical study. [ DOI ]

Pd-catalyzed cross-coupling/heterocyclization domino reaction: facile access to anthra[2,3-b]furan-5,10-dione scaffold / A. S. Tikhomirov, A. E. Shchekotikhin, Y. N. Luzikov et al. // Tetrahedron. — 2014. — Vol. 70, no. 28. — P. 8062–8066. A new facile route to the synthesis of 4,11-dimethoxyanthra[2,3-b]furan-5,10-dione and its novel 2-substituted derivatives was proposed. The developed scheme was based on a Pd-catalyzed cross-coupling/heterocyclization domino reaction of 3-bromo-2-hydroxy-4,11-dimethoxyanthraquinone with terminal alkynes. [ DOI ]

Synthesis and evaluation of new antitumor 3-aminomethyl-4,11-dihydroxynaphtho[2,3-f]indole-5,10-diones / A. E. Shchekotikhin, L. G. Dezhenkova, Y. N. Luzikov et al. // European Journal of Medicinal Chemistry. — 2014. — Vol. 86. — P. 797–805.

ГЕТЕРОЦИКЛИЧЕСКИЕ АНАЛОГИ5,12-НАФТАЦЕНХИНОНА.12.СИНТЕЗ 2-ЗАМЕЩЕННЫХ ПРОИЗВОДНЫХ 4,11-ДИМЕТОКСИ-5,10-ДИОКСОАНТРА[2,3-b]ФУРАН-3-КАРБОНОВЫХ КИСЛОТ / А. С. Тихомиров, А. Е. Щекотихин, Ю. Н. Лузиков и др. // Химия гетероциклических соединений. — 2014. — С. 298–308. [ DOI ]

Тихомиров А. С., Щекотихин А. Е., Преображенская М. Н. Исследование влияния структуры боковой цепи антра[2,3-b]фуранкарбоксамидов на цитотоксические свойства // Российский биотерапевтический журнал. — 2014. — № 2. — С. 133–133.

Тихомиров А. С., Щекотихин А. Е., Преображенская М. Н. МЕТОДЫ СИНТЕЗА И МОДИФИКАЦИИ ЛИНЕЙНЫХ АНТРАФУРАНДИОНОВ (ОБЗОР) // Химия гетероциклических соединений. — 2014. — С. 193–208. [ DOI ]

РАЗРАБОТКА ИНТЕРАКТИВНЫХ МАТЕРИАЛОВ ДЛЯ ТЕСТИРОВАНИЯ И ОБУЧЕНИЯ СТУДЕНТОВ ОРГАНИЧЕСКОЙ ХИМИИ / Н. А. Пожарская, И. В. Иванов, И. О. Акчурин и др. // Успехи в химии и химической технологии. — 2014. — Т. 28, № 9. — С. 99–101.

Разработка интерактивных материалов для тестирования обучения студентов органической химии / Н. А. Пожарская, И. В. Иванов, И. О. Акчурин и др. // Успехи в химии и химической технологии. — 2014. — Т. 14, № 9. — С. 99–101.

Guanidino anthrathiophenediones as g-quadruplex binders: Uptake, intracellular localization, and anti-harvey-ras gene activity in bladder cancer cells / S. Cogoi, A. Membrino, L. E. Xodo et al. // Journal of Medicinal Chemistry. — 2013. — Vol. 56, no. 7. — P. 2764–2778.

Heterocyclic analogs of 5,12-naphthacene-quinone. 11. a new method for preparing 4,11-dimethoxyanthra[2,3-b]furan-5,10-dione / A. S. Tikhomirov, A. E. Shchekotikhin, Y. N. Luzikov et al. // Chemistry of Heterocyclic Compounds. — 2013. — Vol. 49. — P. 241–248. [ DOI ]

Исследование влияния заместителя в положении 2 на биологические свойства противоопухолевых антрафурандионов / А. С. Тихомиров, А. Е. Щекотихин, Л. Г. Деженкова, А. А. Штиль // Российский биотерапевтический журнал. — 2013. — № 2. — С. 83–83.

Heterocyclic analogs of 5,12-naphthacenequinone 10.* synthesis of furanoquinizarine and its new derivatives / A. S. Tikhomirov, A. E. Shchekotikhin, Y. N. Luzikov et al. // Chemistry of Heterocyclic Compounds. — 2012. — Vol. 47, no. 10. — P. 1206–1211. A new method was developed for synthesis of anthra[2,3-b]furan-5,10-dione derivatives. The key compound for annelation of the furan fragment to the anthraquinone chromophor is the previously unknown analog of salicylaldehyde, 1,4-dimethoxy-3-formyl-2-hydroxyanthraquinone, which we have synthesized by the Miller–Loudon–Schneider reaction. A chain of sequential transformations was used for its conversion into the target 4,11-dihydroxyanthra[2,3-b]furan-5,10-dione (furanoquinizarine): O-alkylation of the starting formylhydroxyanthraquinone with bromoacetic acid esters, cyclo-dehydration of the 3-formylanthraquinon-2-ylacetic acid esters in the presence of bases, hydrolysis of the obtained esters to 4,11-dimethoxy-5,10-dioxo-5,10-dihydroanthra[2,3-b]furan-2-carboxylic acid, its decarboxylation, and demethylation of the obtained 4,11-dimethoxyanthra[2,3-b]furan-5,10-dione. [ DOI ]

Тихомиров А. С., Щекотихин А. Е. Новый метод синтеза 4,11-диметоксиантра[2,3-b]фуран-5,10-диона // Успехи в химии и химической технологии. — 2012. — Т. 26, № 5. — С. 76–78.

Disordering of human telomeric g-quadruplex with novel antiproliferative anthrathiophenedione / D. Kaluzhny, N. Ilyinsky, A. Shchekotikhin et al. // PLoS ONE. — 2011. — Vol. 6, no. 11. — P. e27151. Linear heteroareneanthracenediones have been shown to interfere with DNA functions, thereby causing death of human tumor cells and their drug resistant counterparts. Here we report the interaction of our novel antiproliferative agent 4,11-bis[(2-{[acetimido]amino}ethyl)amino]anthra[2,3-b]thiophene-5,10-dione with telomeric DNA structures studied by isothermal titration calorimetry, circular dichroism and UV absorption spectroscopy. New compound demonstrated a high affinity (K(ass)∼10⁶ M⁻¹) for human telomeric antiparallel quadruplex d(TTAGGG)₄ and duplex d(TTAGGG)₄∶d(CCCTAA)₄. Importantly, a ∼100-fold higher affinity was determined for the ligand binding to an unordered oligonucleotide d(TTAGGG TTAGAG TTAGGG TTAGGG unable to form quadruplex structures. Moreover, in the presence of Na+ the compound caused dramatic conformational perturbation of the telomeric G-quadruplex, namely, almost complete disordering of G-quartets. Disorganization of a portion of G-quartets in the presence of K+ was also detected. Molecular dynamics simulations were performed to illustrate how the binding of one molecule of the ligand might disrupt the G-quartet adjacent to the diagonal loop of telomeric G-quadruplex. Our results provide evidence for a non-trivial mode of alteration of G-quadruplex structure by tentative antiproliferative drugs. [ DOI ]

Тихомиров А. С., Щекотихин А. Е. Разработка метода получения 4,11-диметокси-5,10-диоксо-антра[2,3-b]-фуран-2-карбоновой кислоты и синтез ее производных // Успехи в химии и химической технологии. — 2011. — Т. 25, № 4. — С. 17–20.

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