Irina Khan
Verified @gmail.com
Scopus Publications
- Synthesis and Antitumor Potency of 2E,21E-bis-(2-Pyridinylidene)-hollongdione in NCI-60 Panel and Zebrafish Model
Irina Smirnova, Zarema Galimova, Alexander Lobov, Anastasiia Mikheenko, Irina Khan, Gulalek Babayeva, Vadim S. Pokrovsky, Oxana Kazakova
International Journal of Molecular Sciences, 2026
Michael acceptors, such as chalcones and benzylidenes, are privileged scaffolds for the development of anticancer agents. Taking this into account, we developed a selective Claisen–Schmidt condensation of the dammarane-type triterpenoid hollongdione with pyridine-2-carbaldehyde, enabling controlled synthesis of mono- and bis-substituted triterpenes depending on the reaction conditions. The reaction demonstrated high temperature-dependent regioselectivity, providing C2-mono- 2 or 2,21-bis-substituted 3 triterpenes with yields up to 96% and 95%, respectively. The structures of the newly synthesized triterpene chalcones were elucidated by 1D and 2D NMR spectroscopy and unambiguously confirmed by a single-crystal X-ray diffraction, which established the E configuration of the exocyclic double bond. In biological studies, the bis-2-pyridylidene derivative 3 exhibited a pronounced and broad-spectrum antitumor activity in the NCI-60 panel, inducing cell death in 58 of 59 cancer cell lines. High selectivity toward melanoma, renal, and prostate cancer cell lines was observed, with selectivity indices (SI) of up to 18.82 for melanoma LOX IMVI. In MTT assays, compound 3 displayed a submicromolar cytotoxicity, particularly against the KRAS-mutant PANC-1 cell line (IC50 = 0.22 µM). Anticancer activity was further confirmed in a zebrafish (Danio rerio) xenograft model of human HCT116 colon cancer, where tumor growth inhibition reached 72% without pronounced embryotoxicity (LC50 = 1.4 µM). We have developed an efficient approach for the site-selective modification of hollongdione, providing access to potent anticancer dammarane-type chalcones. The bis-2-pyridylidene derivative 3 emerged as a promising lead compound, demonstrating submicromolar potency, high selectivity towards melanoma, and significant in vivo efficacy in a zebrafish xenograft model. - Pt(IV)-BODIPY Nanoparticles for Photoinduced Tumor Ablation and NIR Light-Activated Chemotherapy
Vladislav Bykusov, Ilia Kuzmichev, Yulia A. Isaeva, Maxim Stepanov, Roman A. Akasov, Lin Huang, Si Gao, Kun Qian, Petr V. Gorelkin, Alexander S. Erofeev, Regina Kuanaeva, Aleksey Nikitin, Vita N. Nikitina, Vugara Mamed-Nabizade, Yulia Maksimova, Igor A. Rodin, Mikhail F. Vokuev, Alexander G. Martynov, Dmitry Bunin, Maxim A. Abakumov, Nelly S. Chmelyuk, Polina Lazareva, Vadim S. Pokrovsky, Irina Khan, Elena K. Beloglazkina, Olga O. Krasnovskaya
ACS Applied Nano Materials, 2026
Phototheranostics, which combine light-induced therapeutic and diagnostic modalities in a single platform, is a novel approach in tumor treatment and diagnostics. The development of dual-action nanomaterials with photothermal activity and the ability to act as photoactivated chemotherapy, capable of the light-induced release of chemotherapeutic agents, is a challenging task. However, different nanosystems reported to date represent either photoactivated chemotherapy (PACT), agents of photothermal therapy (PTT), or the loading of a drug and photoabsorber in a single polymer carrier. Herein, we report a near-infrared-light-activatable theranostic nanoplatform CF3-Pt-NPs with dual antitumor action, PTT/PACT, which is also capable of fluorescent and photothermal imaging of tumor tissues, based on the photoactivated Pt(IV) prodrug CF3-Pt with BODIPY in the axial position. A barrier-free CF3 rotor moiety in the BODIPY core provides excellent photothermal efficacy for the nanoplatform, while both the Pt(IV) prodrug CF3-Pt and nanoparticles CF3-Pt-NPs based on it act as PACT agents by releasing cisplatin under 740 nm light irradiation. Metabolomic profiles of CF3-Pt-NP-treated MCF-7 cells confirmed strong thermal- and cisplatin-induced responses of cells. CF3-Pt-NPs demonstrated the ability to accumulate in vivo in tumors, with the degree of fluorescence in the tumor correlating well with platinum accumulation, thereby confirming the ability of CF3-Pt-NPs to reach the tumor intact. A strong photothermal effect in vivo was confirmed after both intratumoral and intravenous administration of CF3-Pt-NPs with 808 nm laser irradiation. This is the first theranostic nanoplatform with dual PTT/PACT antitumor action, which is also capable of fluorescent and photothermal imaging of tumor tissues. - New redox-active Cu complexes with tridentate chelating ligands based on 2-thioimidazol-4-ones as potential antiproliferative agents
Dmitry A. Guk, Georgy L. Karetnikov, Anna A. Moiseeva, Daria A. Ipatova, Uliana G. Alekseechkina, Dmitry A. Skvortsov, Yuri K. Grishin, Victor A. Tafeenko, Konstantin A. Lyssenko, Irina I. Khan, Vadim S. Pokrovsky, Vladimir I. Pergushov, Elena K. Beloglazkina
Dalton Transactions, 2026
New type of copper complexes with antiproliferative properties. - Codelivery of Bortezomib and Modified DR5-Selective TRAIL via Amphiphilic Poly(N-vinylpyrrolidone) Bionanocomposites to Overcome Glioblastoma Resistance
Ekaterina V. Kukovyakina, Pavel P. Kulikov, Dmitry V. Bagrov, Andrey V. Moiseenko, Tatiana S. Trifonova, Alina A. Isakova, Margarita L. Shuvalova, Elena V. Svirshchevskaya, Irina I. Khan, Vadim S. Pokrovsky, Marine E. Gasparian, Andrey N. Kuskov, Anne V. Yagolovich
ACS Applied Bio Materials, 2025
Nanosized carriers based on amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) are a versatile delivery system for various therapeutic agents such as anti-inflammatory drugs and plasmid DNA, as well as targeted antitumor drugs and proteins. Earlier, we developed Amph-PVP-based nanoparticles decorated by a modified DR5-specific TRAIL variant DR5-B (PVP-DR5-B) or containing the proteasomal inhibitor bortezomib (PVP-BTZ). Both DR5-B and BTZ have antitumor properties and, when combined, act synergistically on tumor cells. In the present study, Amph-PVP nanoparticles were loaded with BTZ and subsequently decorated with the TRAIL variant DR5-B, producing a dual polymeric bionanocomposite system PVP-BTZ-DR5-B. Using 2D and 3D in vitro cultures of human glioblastoma cell lines U87MG and T98G, it was demonstrated that PVP-BTZ-DR5-B nanoparticles were internalized and accumulated in cells more efficiently, demonstrating significantly enhanced cytotoxicity compared to free DR5-B or PVP-BTZ nanoparticles loaded with bortezomib alone. PVP-BTZ-DR5-B nanoparticles also penetrated the blood–brain barrier more efficiently than DR5-B in an in vitro model. Finally, the enhanced antitumor effect of PVP-BTZ-DR5-B was demonstrated in a xenograft model of U87MG glioblastoma cells in zebrafish embryos in vivo. Thereby, coloading of BTZ and DR5-B into the Amph-PVP nanoparticles is a promising approach to enhance the antitumor efficacy of free drugs and overcome glioblastoma resistance. - Effect of Ultra-Low Concentrations of Doxorubicin in Biological Nanoparticles in Breast Tumor Models
A. D. Yudaeva, N. I. Ponomareva, S. A. Brezgin, A. S. Frolova, A. P. Kostyusheva, P. A. Demina, D. V. Sokolova, G. Babayeva, I. I. Khan, E. V. Khaydukov, A. Parodi, V. S. Pokrovsky, A. A. Zamyatnin,, V. P. Chulanov, D. S. Kostyushev
Biochemistry Moscow Supplement Series B Biomedical Chemistry, 2025
Abstract To date, chemotherapeutic agents remain the primary method for treating many oncological diseases, including breast cancer (BC). However, numerous side effects caused by the indiscriminate destruction of actively dividing cells limit the safe use of chemotherapeutic agents in clinical practice. Due to the combination of unique properties of nanoparticles, including high biocompatibility and the ability to overcome biological barriers, biological nanoparticles (BNP) are a promising tool for reducing the unwanted toxicity of modern chemotherapeutic agents. This study examined the efficacy of delivering ultra-low concentrations of doxorubicin (0.0544 mg/kg), a dose that is 100 times less than the single therapeutic dose used in a mouse model, using orthotopic and functionalized exosome-like nanoparticles in BC models in vitro and in vivo. It was shown that doxorubicin loaded in BNP exhibited increased cytotoxic activity compared to the free chemotherapeutic agent in vitro. Moreover, a more pronounced activity of functionalized (targeted) nanoparticles towards breast cancer cell receptors was demonstrated compared to orthotopic particles obtained from the tumor. In an in vivo experiment on mice with BC, doxorubicin in ultra-low doses incorporated in BNP did not show an anti-tumor effect; however, there was a trend towards a reduction in tumor nodule size with the administration of orthotopic and functionalized BNP with doxorubicin. Therefore, (1) BNP enhance anti-tumor activity, allowing for a reduced dose of the administered chemotherapeutic agent, (2) the creation of targeted nanoparticles ensures enhanced accumulation of the drug in tumor cells, but (3) ultra-low doses of the chemotherapeutic agent do not have a pronounced effect on BC growth in vivo. The results of the study indicate the potential for using BNP as a strategy to reduce off-target toxicity of modern chemotherapeutic agents. - Biologics-based technologies for highly efficient and targeted RNA delivery
Anastasiya Kostyusheva, Sergey Brezgin, Natalia Ponomareva, Anastasiia Frolova, Alexander Lunin, Ekaterina Bayurova, Andrey Tikhonov, Olga Slatinskaya, Polina Demina, Artyom Kachanov, Gulalek Babayeva, Irina Khan, Dmitry Khochenkov, Yulia Khochenkova, Darina Sokolova, Denis Silachev, Georgy Maksimov, Evgeny Khaydukov, Vadim S. Pokrovsky, Andrey A. Zamyatnin, Alessandro Parodi, Ilya Gordeychuk, Vladimir Chulanov, Dmitry Kostyushev
Molecular Therapy, 2025 - Human Metastatic Melanoma Cell Lines Panel for In Vitro and In Vivo Investigations
Ekaterina N. Kosobokova, Nadezhda A. Kalinina, Ksenia M. Konoplina, Anastasiia A. Malchenkova, Alexandra E. Evdokimova, Marina V. Piniugina, Irina I. Khan, Ilya A. Kislyak, Anna A. Basharina, Anna N. Grishanina, Anna A. Rudakova, Pavel O. Varaksa, Maria A. Baryshnikova, Vadim S. Pokrovsky, Tatiana A. Bogush, Vyacheslav S. Kosorukov
Journal of Molecular Pathology, 2024
The melanoma origin of cell lines obtained from the axillary lymph node (mel Kas, mel Pet, and mel Lap from patients with a verified diagnosis) was confirmed by the detection of the Melan A melanocyte marker expression. A hyperdiploid (2n+) for the mel Kas line; near-diploid (2n), and in some cells near-tertaploid (4n), and even hypo-octaploid (8n) set (172–179 chromosomes) in the mel Pet cell line; and a hypotetraploid (4n−) for the mel Lap line were detected by karyotypic analysis. All three cell lines are tumorigenic; however, mel Pet demonstrates tumor growth in Balb/c nude mice only in the presence of matrigel. All three lines showed a high expression of TUBB3 and PD-L1 markers, while ERa was low (minimum for mel Pet). Significant differences in the expression level were shown for the Cyt molecular marker. In the transplantation of cells to Balb/c nude mice, a stable expression level is observed only for TUBB3. For the rest of the markers, a decrease in their expression level of varying degrees was noted when the cells were growing in solid tumors in vivo. Mutations were detected in oncogenes (BRAF, EZH2, KIT, KRAS, NRAS, ROS1) and tumor suppressor genes (CDKN2A, FAT4, KMT2C, LRP1B, PTEN, PTPRB, TP53). The detailed characterization of the cell lines makes them valuable for various scientific and regulatory experiments, particularly those involving preclinical data on antiproliferative drugs for malignant melanoma or investigations into melanoma cell properties and progression. - Stochastic Packaging of Cas Proteins into Exosomes
N. I. Ponomareva, S. A. Brezgin, A. P. Kostyusheva, O. V. Slatinskaya, E. O. Bayurova, I. V. Gordeychuk, G. V. Maksimov, D. V. Sokolova, G. Babaeva, I. I. Khan, V. S. Pokrovsky, A. S. Lukashev, V. P. Chulanov, D. S. Kostyushev
Molecular Biology, 2024
Abstract—CRISPR/Cas systems are perspective molecular tools for targeted manipulation with genetic materials, such as gene editing, regulation of gene transcription, modification of epigenome etc. While CRISPR/Cas systems proved to be highly effective for correcting genetic disorders and treating infectious diseases and cancers in experimental settings, clinical translation of these results is hampered by the lack of efficient CRISPR/Cas delivery vehicles. Modern synthetic nanovehicles based on organic and inorganic polymers have many disadvantages, including toxicity issues, the lack of targeted delivery, and complex and expensive production pipelines. In turn, exosomes are secreted biological nanoparticles that exhibit high biocompatibility, physico-chemical stability, and the ability to cross biological barriers. Early clinical trials found no toxicity associated with exosome injections. In the recent years, exosomes have been considered as perspective delivery vehicles for CRISPR/Cas systems in vivo. The aim of this study was to analyze the efficacy of CRISPR/Cas stochastic packaging into exosomes for several human cell lines. Here, we show that Cas9 protein is effectively localized into the compartment of intracellular exosome biogenesis, but stochastic packaging of Cas9 into exosomes turns to be very low (~1%). As such, stochastic packaging of Cas9 protein is very ineffective and cannot be used for gene editing purposes. Developing novel tools and technologies for loading CRISPR/Cas systems into exosomes is needed. - Toxicity Evaluation and Controlled-Release of Curcumin-Loaded Amphiphilic Poly-N-vinylpyrrolidone Nanoparticles: In Vitro and In Vivo Models
Anna L. Luss, Dmitry V. Bagrov, Anne V. Yagolovich, Ekaterina V. Kukovyakina, Irina I. Khan, Vadim S. Pokrovsky, Maria V. Shestovskaya, Marine E. Gasparian, Dmitry A. Dolgikh, Andrey N. Kuskov
Pharmaceutics, 2024
Curcumin attracts huge attention because of its biological properties: it is antiproliferative, antioxidant, anti-inflammatory, immunomodulatory and so on. However, its usage has been limited by poor water solubility and low bioavailability. Herein, to solve these problems, we developed curcumin-loaded nanoparticles based on end-capped amphiphilic poly(N-vinylpyrrolidone). Nanoparticles were obtained using the solvent evaporation method and were characterized by dynamic and electrophoretic light scattering, transmission electron (TEM) and atomic force (AFM) microscopy. The average particle size was 200 nm, and the ζ-potential was −4 mV. Curcumin-release studies showed that nanoparticles are stable in aqueous solutions. An in vitro release study showed prolonged action in gastric, intestinal and colonic fluids, consistently, and in PBS. In vitro studies on epidermoid carcinoma and human embryonic kidney cells showed that the cells absorbed more curcumin in nanoparticles compared to free curcumin. Nanoparticles are safe for healthy cells and show high cytotoxicity for glioblastoma cells in cytotoxicity studies in vitro. The median lethal dose was determined in an acute toxicity assay on zebrafish and was 23 μM. Overall, the curcumin-loaded nanoparticles seem promising for cancer treatment. - Stochastic Packaging of Cas Proteins into Exosomes
N. I. Ponomareva, S. A. Brezgin, A. P. Kostyusheva, O. V. Slatinskaya, E. O. Bayurova, I. V. Gordeychuk, G. V. Maksimov, D. V. Sokolova, G. Babaeva, I. I. Khan, V. S. Pokrovsky, A. S. Lukashev, V. P. Chulanov, D. S. Kostyushev
Molekuliarnaia Biologiia, 2024
CRISPR/Cas systems are perspective molecular tools for targeted manipulation with genetic materials, including gene editing, regulation of gene transcription, modification of epigenome etc. While CRISPR/Cas systems proved to be highly effective for correcting genetic disorders and treating infectious diseases and cancers in experimental settings, the clinical translation of these results is hampered by the lack of efficient CRISPR/Cas delivery vehicles. Modern synthetic nanovehicles based on organic and inorganic polymers have many disadvantages, including toxicity issues, the lack of targeted delivery, complex and expensive production pipelines. In turn, exosomes are secreted biological nanoparticles exhibiting high biocompatibility, physico-chemical stability, and ability to cross biological barriers. Early clinical trials found no toxicity associated with exosome injections. In recent years, exosomes have been considered as perspective delivery vehicles for CRISPR/Cas systems in vivo. The aim of this study was to analyze the efficacy of CRISPR/Cas stochastic packaging into exosomes at several human cell lines. Here, we show that Cas9 protein is effectively localized into the compartment of intracellular exosome biogenesis, but stochastic packaging of Cas9 into exosomes turns to be very low (~1%). As such, stochastic packaging of Cas9 protein is very ineffective, and cannot be used for gene editing purposes. Developing novel tools and technologies for loading CRISPR/Cas systems into exosomes is required. - Assessment of the effects of amphiphilic poly (N-vinylpyrrolidone) nanoparticles loaded with bortezomib on glioblastoma cell lines and zebrafish embryos
Anne Yagolovich, Andrey Kuskov, Pavel Kulikov, Dmitry Bagrov, Polina Petrova, Ekaterina Kukovyakina, Alina Isakova, Irina Khan, Vadim Pokrovsky, Alexander Nosyrev, Polyxeni Stamati, Elena Markvicheva, Marine Gasparian, Demetrios Spandidos, Aristidis Tsatsakis
Biomedical Reports, 2024 - Design and Synthesis of New Agents for Prostate Cancer Treatment Inspired by Steroidal CYP17 A1 Inhibitors
Vladimir A. Zolottsev, Alexandra S. Latysheva, Irina I. Khan, Vadim S. Pokrovsky, Alexander Y. Misharin
Chemistryselect, 2022 - Synthesis and Preclinical Evaluation of Small-Molecule Prostate-Specific Membrane Antigen-Targeted Abiraterone Conjugate
Aleksei E. Machulkin, Ekaterina A. Nimenko, Nikolay U. Zyk, Anastasiia A. Uspenskaia, Galina B. Smirnova, Irina I. Khan, Vadim S. Pokrovsky, Alexander N. Vaneev, Roman V. Timoshenko, Vugara V. Mamed-Nabizade, Maria V. Zavertkina, Alexander Erofeev, Petr Gorelkin, Alexander G. Majouga, Nikolay V. Zyk, Elena S. Khazanova, Elena K. Beloglazkina
Molecules, 2022 - Antiproliferative, proapoptotic, and tumor-suppressing effects of the novel anticancer agent alsevirone in prostate cancer cells and xenografts
Irina I. Khan, Saida S. Karshieva, Darina V. Sokolova, Tatiana S. Spirina, Vladimir A. Zolottsev, Alexandra S. Latysheva, Natalia Y. Anisimova, Marina V. Komarova, Marina N. Yakunina, Tatiana A. Nitetskaya, Alexander Y. Misharin, Vadim S. Pokrovsky
Archiv Der Pharmazie, 2022 - Mechanisms of the Antiproliferative and Antitumor Activity of Novel Telomerase-Carbonic Anhydrase Dual-Hybrid Inhibitors
Anna A. Plyasova, Emanuela Berrino, Irina I. Khan, Alexander V. Veselovsky, Vadim S. Pokrovsky, Andrea Angeli, Marta Ferraroni, Claudiu T. Supuran, Marina V. Pokrovskaya, Svetlana S. Alexandrova, Yulia A. Gladilina, Nikolay N. Sokolov, Abdullah Hilal, Fabrizio Carta, Dmitry D. Zhdanov
Journal of Medicinal Chemistry, 2021 - Promising applications of steroid сonjugates for cancer research and treatment
Vladimir А. Zolottsev, Аlexandra S. Latysheva, Vadim S. Pokrovsky, Irina I. Khan, Alexander Y. Misharin
European Journal of Medicinal Chemistry, 2021 - Novel nitrogen containing steroid derivatives for prostate cancer treatment
Alexandra S. Latysheva, Vladimir A. Zolottsev, Vadim S. Pokrovsky, Irina I. Khan, Alexander Yu. Misharin
Current Medicinal Chemistry, 2021 - STEROID CONJUGATES AS POTENTIAL ANTI-CANCER AGENTS
V. A. Zolottsev, A. S. Latysheva, V. S. Pokrovsky, I. I. Khan, R. L. M. Almanza, A. Y. Misharin
Rossijskij Bioterapevticeskij Zurnal, 2020
