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Преподаватели и сотрудники

Тихомиров Александр Сергеевич

Тихомиров Александр Сергеевич

Занимаемые должности

Ассистент (Кафедра органической химии)

Телефон

(499) 978-59-46

E-mail

atikhomirov@muctr.ru

Сайт https://muctr.ru
Уровень образования Высшее
Квалификация

Преподаватель органической химии

Преподаваемые дисциплины

Органическая химия (1.2)

Практикум по органической химии

Учёная степень

Кандидат химических наук

Наименование направления подготовки и (или) специальности

Химическая технология синтетических биологически активных веществ

Общий стаж работы 5 лет (с 01.01.2014)
Стаж работы по специальности 3 года (с 01.11.2015)

Публикации

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 ]

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 ]

Design of an activity-based probe for human neutrophil elastase: Implementation of the lossen rearrangement to induce förster resonance energy transfers / S.-F. Anna-Christina, A. S. Tikhomirov, B. Annett et al. // Biochemistry. — 2018. — Vol. 57. — P. 742–752. Human neutrophil elastase is an important regulator of the immune response and plays a role in host defense mechanisms and further physiological processes. The uncontrolled activity of this serine protease may cause severe tissue alterations and impair inflammatory states. The design of an activity-based probe for human neutrophil elastase reported herein relies on a sulfonyloxyphthalimide moiety as a new type of warhead that is linker-connected to a coumarin fluorophore. The inhibitory potency of the activity-based probe was assessed against several serine and cysteine proteases, and the selectivity for human neutrophil elastase (Ki = 6.85 nM) was determined. The adequate fluorescent tag of the probe allowed for the in-gel fluorescence detection of human neutrophil elastase in the low nanomolar range. The coumarin moiety and the anthranilic acid function of the probe, produced in the course of a Lossen rearrangement, were part of two different Förster resonance energy transfers. [ 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 ]

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