The review covers research on dual-target antitumor agents over the past five years. One of the targets is histone deacetylases (HDACs), while the second potential target is a protein group located both on the membrane surface (phosphatidylinositol 3-kinase (PI3K), anaplastic lymphoma kinase (ALK), receptor tyrosine kinase (AXL), tyrosine protein kinase (HER2), FMS-like tyrosine kinase (FLT3), and vascular endothelial growth factor receptor (VEGFR2)) and in the nucleus (serine/threonine protein kinase Wee1, DNA methyltransferase (DNMT), dual-specificity phosphatase (CDC25A), an enzyme from the cyclin-dependent kinase family (CDK9), dual-specificity tyrosine-serine/threonine kinase (DYRK2), and BET family proteins (BRD4, BD1, and BD2)). This review presents the results of studies on the inhibitory activity of various HDAC isoforms and other enzymes, as well as in vitro cytotoxicity studies on both neoplastic and healthy cells. It also includes selectivity studies, in vivo experiments (changes in tumor volume in mice) and oral bioavailability assessments. The review also describes the chemical structures of several dual-target agents and identifies the molecular fragments responsible for inhibiting different targets. Based on the studies reviewed in this paper, it can be concluded that some dual inhibitors have superior in vitro cytotoxicity and exhibit selectivity towards some tumor cells compared to monofunctional reference compounds. These findings may be useful for molecular design in the field of polypharmacology, with the aim of developing new dual-target molecules that exhibit improved antitumor activity and selectivity towards neoplastic cells.

In this study, a simple and efficient method for the synthesis of conjugates of N-acyl derivatives of 3,5-bis(benzylidene)-4-piperidones and phenothiazine was developed. The method was based on the acylation of 3,5-bis(benzylidene)-4-piperidones with chloroacetic acid chloride, followed by treatment of the product with sodium azide and an azide-alkyne [3+2] cycloaddition reaction between the resulting azide and 10-(prop-2-yn-1-yl)-10H-phenothiazine in the final step. Using this method, a series of seven compounds 23-29 were synthesized. The structure of synthesized compounds 23-29 was studied using 1H, 13C, and 19F NMR spectroscopy and ESI-MS mass spectrometry. The cytotoxicity of compounds 23-29 and their hydrochloride salts 30-36 towards pancreatic adenocarcinoma Panc-1, bladder cancer T-24, glioblastoma T98G, breast adenocarcinoma BT-20, and normal dermal fibroblast DF-1 cells was studied using an MTT assay. Compound 29, containing 3,4,5-trimethoxyl radicals at the aromatic ring, and its hydrochloride salt 36, demonstrated the best cytotoxicity against Panc-1, T-24, T98G, and BT-20 cancer cells. Hydrochloride salts were found to exhibit superior cytotoxicity against Panc-1, T-24, T98G, and BT-20 cancer cells compared to the original 3,5-bis(benzylidene)-4-piperidones and free bases. Selective cytotoxic action against Panc-1, T-24, T98G, and BT-20 cancer cells compared to normal DF-1 cells was also observed for all the obtained compounds and their salts.

A strategy to create highly effective antimicrobial agents was proposed based on the conjugation of three functional components: a cationic quaternary ammonium salt (QAS) that exerts a membrane-disrupting effect and promotes selective accumulation on bacterial surfaces; a phosphonamidate linker for controlled activation; and a sterically hindered phenol (SHP) fragment as a potential redox component. This approach enabled the preparation of 40 target phosphonamidate-SHP/QAS hybrids in high yields (88-98%). Evaluation of their antimicrobial activity against major pathogens and methicillin-resistant Staphylococcus aureus (MRSA) revealed high potency against Gram-positive bacteria. The lead compounds achieved minimum inhibitory concentration (MIC) values of 0.7-2.8 μM, which is up to 10 times lower than that of the reference drug, norfloxacin. Mechanistic studies confirmed that these hybrids disrupt the bacterial membrane. In addition, an increase in intracellular ROS levels was observed for the most active compound. The SHP/QAS hybrids retained high activity against S. aureus ATCC 209P after 17 passages and showed low cytotoxicity (SI = 62-92) and negligible hemolysis. These properties indicate that this approach may offer a useful strategy for developing antibacterial agents with a potentially lower risk of inducing conventional resistance mechanisms.

This review examines publications over the past two years devoted to histone deacetylase inhibitors for the treatment of cancer, diseases of the nervous, cardiovascular, digestive, and respiratory systems, and autoimmune diseases. The review covers various classes of histone deacetylase inhibitors depending on the zinc-binding group, in particular hydroxamic acids, benzamides, hydrazides, carboxylic acids, and cyclic peptides. The review pays special attention to the mechanisms of development of pathologies involving various isoforms of histone deacetylases. The review shows that, for the treatment of cancer, nervous, cardiovascular, respiratory systems, and autoimmune diseases, the most promising compounds are hydroxamic acids, and for the treatment of diseases of the digestive system, they are hydrazides and cyclic peptides. Variation in the linker and cap group of hydroxamic acids will allow the creation of an inhibitor selective for a specific histone deacetylase isoform. The review may be useful for molecular biologists, medical workers, and pharmacologists involved in the design of new drugs.

This review is devoted to research in the field of photodynamic and photothermal therapies for malignant tumors. Special attention in the review is given to photosensitizers based on compounds with a tetrapyrrole ring system, their metal complexes, BODIPY and aza-BODIPY derivatives, squaraines, and photoactivators based on metal complexes with other ligands such as phenanthroline and its derivatives, metronidazole, pyridine, and imidazole derivatives. Additionally, the review considers nanosized carriers for photosensitizers, such as organic and inorganic nanoparticles, liposomes, and extracellular vesicles. This review also discusses the dark toxicity and phototoxicity of these compounds and the processes of free oxygen radical formation, mitochondrial dysfunction, and induction of apoptosis in cancer cells. It has been established that nanoscale delivery systems are more promising for use in photodynamic and photothermal therapy compared to molecular photosensitizers. This is due to their improved solubility in physiological environments, selective accumulation in tumors, prolonged photoactivity, and lower therapeutic dose, which allows for the minimization of the side effects of treatment. Among the molecular photosensitizers under consideration, amphiphilic tetrapyrroles appear to be the most promising. Specifically, tetrapyrrole complexes of indium (III) and iridium (III) with non-porphyrin ligands exhibit favorable photophysical and biological characteristics. The review also indicates that photosensitizers tend to localize in the mitochondria of tumor cells, contributing to oxidative stress and apoptosis activation. This review may be of interest to biochemists and oncologists.

To develop new hybrid anticancer agents, 3,5-bis(benzylidene)-4-piperidone scaffolds (compounds 1–6) were functionalized with (1R)-borneoyl chloroacetate (8) or (1S)-camphorsulfonyl chloride (10). Covalent attachment of the camphorsulfonyl moiety via N-sulfonylation yielded hybrid molecules (16–21) that exhibited selective cytotoxic and cytostatic activity against cancer cells, with submicromolar IC50 values. In silico ADME analysis indicated that these camphorsulfonyl-conjugated piperidones have improved drug-like properties (enhanced absorption, metabolism, and bioavailability) compared to curcumin. The most potent analogs were halogen-substituted and trimethoxy-substituted analogs, which showed the strongest tumor cell growth inhibition while sparing normal cells. Overall, this terpene-functionalization strategy addresses curcumin’s pharmacokinetic limitations and improves its anticancer profile. These hybrid molecules hold promise as potential anticancer agents.

In this study, we present the synthesis of four novel Cu(II) complexes based on podands with terminal 8-oxyquinolyl groups and evaluation of their potential anticancer activity. The syntheses of ligands were achieved by a unified procedure in which 1,5-bis(8-oxyquinolyl)-3-oxapentane (L1), 2,6-bis((8-oxyquinolyl)methyl)pyridine (L2), 1,8-bis(8-oxyquinolyl)-3,6-dioxaoctane (L3) were prepared by a one-step reaction of 2 equiv. of 8-hydroxyquinoline sodium salt with diethylene glycol ditosyl, 2,6-bis(tosylatemethyl)pyridine and triethylene glycol ditosyl, respectively, in good yields. The synthesis of copper(II) complexes [Cu2L1Br2(mu -OCH3)2] (1), [Cu2L1Br2(mu -OH)(mu -Br)] (2), [Cu2L1Br2(mu -Br)2]& sdot;CH3CN (3), and [CuL2Br]Br (4) was performed through the reaction of CuBr2 with L1 and L2 ligands under mild conditions. Single crystal X-ray diffraction analysis revealed that complexes 1-3 possessed binuclear structures, while complex 4 exhibited a mononuclear configuration. The in vitro anticancer activities of the four complexes were evaluated against four different cancer cell lines. The complexes exhibited higher activity compared to their respective free ligands, inducing cell growth inhibition and apoptosis in a concentration-dependent manner. Compounds 3 and 4 exhibited the most pronounced cytotoxic effect against the A549 cell line, with IC50 values of 21.43 +/- 0.20 and 30.67 +/- 2.23 mu M, respectively. It is also noteworthy that lower IC50 values were observed for all compounds against Hek-293 cells of normal origin. A selectivity index of 2 was calculated for compound 3. According to study of the effect on apoptosis, compounds 1 and 4 at the selected concentration after 24 h significantly increased the percentage of the apoptotic population. Confocal microscopy revealed that all the synthesized complexes penetrate into the cells and localize in the perinuclear space. It is suggested that aberrant glycolysis is one of the primary targets of the action of Cu(II) complexes 1-4, and the detected cytotoxic activity appears to be related to the ability of 1-4 to alter the pathological mechanism of tumor cell metabolism.

To date, the use of classical antibacterial purification schemes in the oil and gas industry is under threat due to the frequent resistance of bacteria to a limited number of biocidal treatment programs. In this regard, the potential of synthetic molecules as biocidal agents is being actively studied worldwide. In this study, benzofuroxans were considered for rational control of microbial contamination in industry, for which derivatives a wide range of antimicrobial activity are currently known, particularly against multidrug-resistant strains. Previously, these compounds with morpholine fragments and a fragment of N-dimethylpropylamine demonstrated the highest cytotoxic activity, correlating well with their ability to inhibit the glycolysis process in tumor cells. Water-soluble salts based on them showed good effectiveness in the pre-sowing treatment of crop seeds, and in some cases, the seed treatment with these salts led not only to improved seed germination, but also to the suppression of microflora growth. Using a panel of tests, the ability of benzofuroxan with the morpholine fragment 4b to significantly reduce the levels of aerobic and anaerobic bacteria was revealed, which encourages its further study as a biocide. Thus, the results indicate the significant potential of benzofuroxans with amine groups for use in the oil and gas industry for wastewater treatment.

New 4-hydroxycoumarins and coumestans with tert-butyl and isobornyl substituents were synthesized. The cytotoxic profile and the antioxidant status of the synthesized compounds were assessed using in vitro models. The promise of the coumestans studied as potential antitumor agents is demonstrated. A possible mechanism of the action of the title compounds is associated with the antioxidant activity expressed in the ability to inhibit the process of lipid peroxidation and with the direct antiradical activity in the ORAC and DPPH assays.

An effective method for synthesizing dihalogenated derivatives of condensed benzimidazole diones with a nodal nitrogen atom has been developed. As a result, five new heterocyclic quinones were obtained, which differed in the structure of the heterocycle annelated to imidazole, as well as the nature and arrangement of halogen atoms. A comprehensive analysis of the anticancer potential of new heterocyclic quinones revealed pronounced cytotoxic activity of the molecules against tumor cells. Using in silico methods for predicting activity spectra, it was found that the synthesized compounds are capable of interacting with a number of key targets that play an important role in oncogenesis, with the highest probability of binding to STAT3, the central regulator of cell growth, proliferation and metabolism. Experimental studies have shown that, despite the lack of pronounced ability to induce apoptosis, these substances effectively inhibit the activity of allosteric glycolytic enzymes, disrupting metabolic adaptation and energy balance of tumor cells. The obtained results expand the understanding of the molecular basis of the antitumor action of heterocyclic compounds and lay a solid foundation for their use as promising modulators of tumor cell metabolism.

BACKGROUND:Hormone signaling plays a significant role in cancerogenesis. This review presents a comprehensive analysis of FDA-approved drugs, as well as recent clinical trials of drugs acting on hormone signaling pathways. It discusses traditional methods of hormonal cancer therapy and identifies new mechanisms in cancer hormonal signaling. The review has made use of the databases Clinicaltrials.gov and PubMed to find new trends in the development of anti-cancer drugs and related hormonal-dependent mechanisms of breast cancer. METHODS:A search of the Drugs@FDA database was conducted to identify pharmaceutical agents approved by the FDA for the treatment of hormone-dependent breast tumors. The clinical trials for these drugs were obtained from ClinicalTrials.gov. The search was expanded from 2018 to early 2024. The keywords used in the search for information were breast cancer, hormonal signaling pathways, luminal types of breast cancer, and hormone-dependent breast cancer. The drug targets, pharmacological information, and clinical data were obtained from the PubMed database. RESULTS:An analysis of the ClinicalTrials.gov database revealed that the pharmacokinetic direction has significant potential for the discovery of new drugs. The metabolites of SERMs metabolites and their combination have the potential to enhance the efficiency of prodrug. Small molecules can penetrate through the blood-brain-barrier, making them a promising avenue for treating brain metastasis. New SERDs, such as ZB716, exhibit superior oral bioavailability compared to fulvestrant, which is solely administered via injection. The investigation of the signaling hormonal pathways of BC allows for the enhancement of personalised anti-cancer therapy and the overcoming of resistance. Consequently, the specific mechanism of action of ARV-471 (the PROTAC group) enhances sensitivity to drug-resistant targets and affects non-enzymatic functions. Furthermore, PROTACs exhibit markedly enhanced target selectivity in comparison to traditional inhibitors. The combination of endocrine therapy for breast cancer with compounds that target mTOR, PI3K, CDK4/6, and other pathways holds considerable promise. The combination of letrozole with everolimus demonstrated the most promising outcome, with a median progression-free survival period of 22 months, a significant improvement over the 9-month median progression-free survival observed in monotherapy with letrozole. CONCLUSION:It is evident that traditional endocrine treatments play a pivotal role in the management of HR+ BC. However, the emergence of resistance necessitates the development of novel therapeutic strategies. These strategies should be based on pharmacokinetics, further investigation of the molecular signaling pathways of BC, such as new SERMs, SERDs, PROTACs, as well as new drug groups, like SERCAs, CERANs, SHERPAs. Combination therapy represents the most promising avenue for BC treatment. While PROTAC combination with new monotherapeutic agents for BC treatment has yet to be investigated, we believe that such combinations have the potential to make the treatment more selective, effective, and personalised in the future.

Chemotherapy with anthracycline antibiotics is a common method of treating tumors of various etiologies. To create more highly effective cytostatics based on daunorubicin, we used the method of reductive amination using polyalkoxybenzaldehydes. The obtained derivatives of the anthracycline structure have much greater cytotoxicity compared to daunorubicin due to increased affinity for DNA, the ability to disrupt the cell cycle, and their inhibition of the glycolysis process, which is confirmed by data from extensive biological studies and the results of molecular modeling.

A simple method for modifying sesquiterpene lactones with 3,5-bis(arylidene)piperi-din-4-ones using the phase-transfer catalytic aza-Michael addition in the MeCN—K2CO3 system was developed. Molecular docking revealed that the synthesized conjugates of isoalantolactone, alantolactone, and dehydrocostus lactone with various bis(arylidene)-piperidones directly interact with the DNA binding site of the p50 subunit of nuclear factor κB, which may be indicative of their ability to induce apoptotic death of the tumor cells due to activation of the death receptor expression and, thereby, to exhibit an antitumor effect.

Aging is a general biological process inherent in all living organisms. It is characterized by progressive cellular dysfunction. For many years, aging has been widely recognized as a highly effective mechanism for suppressing the progression of malignant neoplasms. However, in recent years, increasing evidence suggests a "double-edged" role of aging in cancer development. According to these data, aging is not only a tumor suppressor that leads to cell cycle arrest in neoplastic cells, but also a cancer promoter that ensures a chronic proinflammatory and immunosuppressive microenvironment. In this regard, in our review, we discuss recent data on the destructive role of senescent cells in the pathogenesis of cancer. We also identify for the first time correlations between the modulation of the senescence-associated secretory phenotype and the antitumor effects of naturally occurring molecules.

BACKGROUND:Sesquiterpene lactones are secondary plant metabolites with a wide variety of biological activities. The process of lactone conjugation to other pharmacophores can increase the efficacy and specificity of the conjugated agent effect on molecular targets in various diseases, including brain pathologies. Derivatives of biogenic indoles, including neurotransmitter serotonin, are of considerable interest as potential pharmacophores. Most of these compounds have neurotropic activity and, therefore, can be used in the synthesis of new drugs with neuroprotective properties.AIM:The aim of this experimental synthesis was to generate potential treatment agents for Alzheimer's disease using serotonin conjugated with natural sesquiterpene lactones.METHODS:Three novel compounds were obtained via the Michael reaction and used for biological testing. The obtained conjugates demonstrated complex neuroprotective activities. Serotonin conjugated to isoalantolactone exhibited strong antioxidant and mitoprotective activities.RESULTS:The agent was also found to inhibit β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), prevent the aggregation of β-amyloid peptide 1-42, and protect SH-SY5Y neuroblastoma cells from neurotoxins such as glutamate and H2O2. In a transgenic animal model of Alzheimer's disease (5xFAD line), the conjugated agent restored declined cognitive functions and improved learning and memory.CONCLUSION:In conclusion, the obtained results indicate that serotonin conjugates to sesquiterpene lactones are promising agents for the treatment of symptoms associated with Alzheimer's disease.

BACKGROUND:Gliomas and glioblastomas (GBM) are common primary malignant brain tumors, which are highly malignant and have a poor prognosis. The presence of cancer stem cells with unrestricted proliferative capacity and ability to generate glial neoplastic cells, the diffuse nature of GBM, and other specific factors of GBM contribute to poor results of drug therapy in patients with GBM. Despite the worldwide efforts to improve the treatment, many novel anti-GBM drugs are active just in vitro, in silico, and in preclinical trials, and they sometimes demonstrate poor or no activity in clinical trials. In this paper, we have casually selected and analyzed the most promising evidence-based results related to glioblastoma treatment at FDA and Clinical Trials.gov databases. It was observed that the most prospective trend in the development of anti-GBM drugs is combination therapy vs. monotherapy. Our analysis of clinical trials has allowed us to predict that the most promising combination therapy that has shown the best results in patient's surveillance should include drugs that block different growth-promoting signals in glioblastoma cells and that are activated by the V600E BRAF mutation. One drug should inhibit signals from the BRAF protein, whereas the second drug in combination should inhibit signals from the MEK protein. METHODS:The content of this review is based on information obtained from PubMed, ClinicalTrials.- gov, and the U.S. Food and Drug Administration (https://www.fda.gov/). In ClinicalTrials.gov, we retrieved studies published from January 1, 2015. In the data search, "Glioblastoma" was used as the keyword. A study was deleted if it studied remedies for concomitant tumor diseases, as well as if it did not include descriptions of treatment methods and/or if GBM was not mentioned. The analysis of the effectiveness of treatment was carried out according to the increasing overall survival in GBM patients, compared to the gold standard for this cancer. RESULTS:GBM patients treated with novel immunotherapy agents and drugs acting on epigenetic factors and receptor tyrosine kinase inhibitors have shown encouraging potential for future development in clinic. However, combinations of drugs have led to more significant improvements in the results and an increase in life expectancy of patients. For example, the combination of nivolumab and ipilimumab showed a 72% increase in life expectancy compared to using nivolumab alone (9.8 vs. 16.85). CONCLUSION:Combining anti-GBM drugs appears to be a key direction for increasing treatment effectiveness and overall survival. Radiotherapy of GBM can increase the effect of combination drug therapy.

Here, we report the results of an investigation of the neuroprotective effects of securinine with tryptamine conjugate-allomargaritarine (2b), previously selected as the leading compound among a wide range of natural derivatives. 2b was synthesized from securinine using various Lewis acids as catalysts. In addition to the antioxidant and cytoprotective properties previously shown for 2b, in this work, in vitro analysis of the biological activity of the compound demonstrated that this conjugate is also able to influence the primary pathogenetic mechanism of Alzheimer's disease - proteinopathy, modulating the homeostasis of β-amyloid peptide. In particular, it was found that 2b is an effective inhibitor of β-secretase 1 - an enzyme responsible for initiating the generation of pathological forms of β-amyloid peptide, as well as directly preventing the pathological aggregation of Aβ1-42. As a compound with a promising biological activity profile found in vitro, 2b has also demonstrated excellent neuroprotective effects on the in vivo 5xFAD Alzheimer's disease transgenic mice model. Thus, 2b effectively restored cognitive dysfunction: short-term and long-term episodic and spatial memory, which in the post-mortem studies was also accompanied by a decrease in the number of amyloid deposits and the intensity of oxidative stress in brain samples. These results provide an opportunity to draw a line under years of research on the neuroprotective potential of 2b as a viable therapy for Alzheimer's disease.

A series of new isatin-3-hydrazones bearing different ammonium fragments was synthesized by a simple and easy work-up reaction of Girard’s reagents analogs with 1-(3,5-di-tert-butyl-4-hydroxybenzyl)isatin. All derivatives have been shown to have antioxidant properties. In terms of bactericidal activity against gram-positive bacteria, including methicillin-resistant strains of Staphylococcus aureus, the best compounds are 3a, 3e, and 3m, bearing octyl, acetal, and brucine ammonium centers, respectively. In addition, brucine and quinine derivatives 3l, and 3j exhibit platelet antiaggregation activity at the level of acetylsalicylic acid, and this series of isatin derivatives does not adversely affect the hemostasis system as a whole. Thus, all the obtained results can lay the groundwork for future pharmaceutical developments for the creation of effective antibacterial drugs with reduced systemic toxicity due to the presence of antioxidant properties.

Anticancer immune surveillance and immunotherapies trigger activation of cytotoxic cytokine signaling, including tumor necrosis factor-α (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) pathways. The pro-inflammatory cytokine TNF-α may be secreted by stromal cells, tumor-associated macrophages, and by cancer cells, indicating a prominent role in the tumor microenvironment (TME). However, tumors manage to adapt, escape immune surveillance, and ultimately develop resistance to the cytotoxic effects of TNF-α. The mechanisms by which cancer cells evade host immunity is a central topic of current cancer research. Resistance to TNF-α is mediated by diverse molecular mechanisms, such as mutation or downregulation of TNF/TRAIL receptors, as well as activation of anti-apoptotic enzymes and transcription factors. TNF-α signaling is also mediated by sphingosine kinases (SphK1 and SphK2), which are responsible for synthesis of the growth-stimulating phospholipid, sphingosine-1-phosphate (S1P). Multiple studies have demonstrated the crucial role of S1P and its transmembrane receptors (S1PR) in both the regulation of inflammatory responses and progression of cancer. Considering that the SphK/S1P/S1PR axis mediates cancer resistance, this sphingolipid signaling pathway is of mechanistic significance when considering immunotherapy-resistant malignancies. However, the exact mechanism by which sphingolipids contribute to the evasion of immune surveillance and abrogation of TNF-α-induced apoptosis remains largely unclear. This study reviews mechanisms of TNF-α-resistance in cancer cells, with emphasis on the pro-survival and immunomodulatory effects of sphingolipids. Inhibition of SphK/S1P-linked pro-survival branch may facilitate reactivation of the pro-apoptotic TNF superfamily effects, although the role of SphK/S1P inhibitors in the regulation of the TME and lymphocyte trafficking should be thoroughly assessed in future studies.

A series of tribenzo[g,l,q]-6H-1,4-diazepino[2,3-b]porphyrazines has been synthesized. A temperature-dependent steric effect was applied in the mixed Linstead macrocyclization of phthalonitrile and 5,7-bis(2'-arylethenyl)-6-propyl-6H-1,4-diazepine-2,3-dicarbonitrile to achieve high yield of low-symmetry A3B-type Mg(II) tribenzo[g,l,q]-6H-1,4-diazepino[2,3-b]porphyrazinate. The analysis of photophysical and photochemical properties of the obtained complexes showed the anti-Kasha effect: the ultrafast spin changes successfully compete with the IC. TD-DFT calculations showed that the presence of 1,4-diazepine heterocycle in the porphyrazine structure leads to the formation of additional charge-transfer triplet state T2. We propose, it could participate in the pumping of T1x state alongside with T1y state (these states are degenerate in D4h symmetry) and, therefore, increase singlet oxygen (1Δg) generation. Stable micellar nanoparticles have been obtained based on the tribenzo[g,l,q]-6H-1,4-diazepino[2,3-b]porphyrazine Mg(II) and Zn(II) complexes using polyvinylpyrrolidone. The nanoparticles effectively interact with model biological structures (FBS and brain homogenate), leading to disaggregation of the macrocycles. They also exhibit pronounced phototoxic effects in MCF-7 cells upon red light irradiation. We propose that enhancement in PDT activity could be explained by their increased resistance to aggregation due to the presence of n-propyl substituent directly attached to the C6 position of the 1,4-diazepine moiety. The demonstrated results show the promising potential of tribenzo-6H-1,4-diazepinoporphyrazines as heavy atom-free photosensitizers.