A Study on the Biological Activity of Optically Pure Aziridine Phosphines and Phosphine Oxides.

A series of optically pure aziridine phosphines and their corresponding phosphine oxides were synthesized through established chemical methodologies. The compounds were systematically investigated for their biological properties. Notably, all synthesized compounds demonstrated moderate antibacterial activity only against the reference strain of Staphylococcus aureus. However, compounds 5 and 7 exhibited noteworthy cell viability inhibition of human cervical epithelioid carcinoma HeLa cells and endometrial adenocarcinoma Ishikawa cells. Further studies of these compounds revealed additional biological effects, including disruption of the cell membrane in high concentrations, cell cycle arrest in the S phase, and the induction of reactive oxygen species (ROS). Comparative analysis of the two classes of chiral organophosphorus derivatives of aziridines indicated that chiral phosphine oxides displayed significantly higher biological activity. Consequently, these findings suggest that chiral phosphine oxides may be potential candidates for the development of anticancer drugs. In light of the significant interest in preparations whose structure is based on a three-membered aziridine ring in terms of potential anticancer therapy, this research fits into the current research trend and should constitute a valuable addition to the current state of knowledge and the existing library of aziridine derivatives with anticancer properties.

Carboranyl-1,8-naphthalimide intercalators induce lysosomal membrane permeabilization and ferroptosis in cancer cell lines.

The synthesis of carborane-1,8-naphthalimide conjugates and evaluation of their DNA-binding ability and anticancer activity were performed. A series of 4-carboranyl-3-nitro-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, were synthesised via amidation and reductive amination reactions, and their calf thymus DNA (ct-DNA)-binding properties were investigated using circular dichroism, UV-vis spectroscopy, and thermal denaturation. Results showed that conjugates 34-37 interacted very strongly with ct-DNA (ΔTm = 10.00-13.00 °C), indicating their ability to intercalate with DNA, but did not inhibit the activity of topoisomerase II. The conjugates inhibited the cell growth of the HepG2 cancer cell line in vitro. The same compounds caused the G2M phase arrest. Cell lines treated with these conjugates showed an increase in reactive oxygen species, glutathione, and Fe2+ levels, lipid peroxidation, and mitochondrial membrane potential relative to controls, indicating the involvement of ferroptosis. Furthermore, these conjugates caused lysosomal membrane permeabilization in HepG2 cells but not in MRC-5 cells.

Novel Antimicrobial Peptides from Saline Environments Active against E. faecalis and S. aureus: Identification, Characterisation and Potential Usage.

Microorganisms inhabiting saline environments have been known for decades as producers of many valuable bioproducts. These substances include antimicrobial peptides (AMPs), the most recognizable of which are halocins produced by halophilic Archaea. As agents with a different modes of action from that of most conventionally used antibiotics, usually associated with an increase in the permeability of the cell membrane as a result of a formation of channels and pores, AMPs are a currently promising object of research focused on the investigation of antibiotics with non-standard modes of action. The aim of this study was to investigate antimicrobial activity against multidrug-resistant human pathogens of three peptides, which were synthetised based on sequences identified in metagenomes from saline environments. The investigations were performed against Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. Subsequently, the cytotoxicity and haemolytic properties of the tested peptides were verified. An in silico analysis of the interaction of the tested peptides with molecular targets for reference antibiotics was also carried out in order to verify whether or not they can act in a similar way. The P1 peptide manifested the growth inhibition of E. faecalis at a MIC50 of 32 µg/mL and the P3 peptide at a MIC50 of 32 µg/mL was shown to inhibit the growth of both E. faecalis and S. aureus. Furthermore, the P1 and P3 peptides were shown to have no cytotoxic or haemolytic activity against human cells.

Biological Activity of fac-[Re(CO)3(phen)(aspirin)], fac-[Re(CO)3(phen)(indomethacin)] and Their Original Counterparts against Ishikawa and HEC-1A Endometrial Cancer Cells.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are inhibitors of cyclooxygenase enzyme (COX) and were found to have positive effects in reducing the risk of developing gynecological cancers. However, long-term administration of NSAIDs carries the risk of various side effects, including those in the digestive and circulatory systems. Therefore, there is a constant need to develop new NSAID derivatives. In this work, we investigated rhenium NSAIDs, comparing their effects on endometrial cancer cells with original NSAIDs, demonstrating the high activity of aspirin and indomethacin derivatives. The cytotoxic activity of rhenium derivatives against the Ishikawa and HEC-1A cancer cell lines was higher than that of the original NSAIDs. The IC50 after 24-h incubation of Ishikawa and HEC-1A were 188.06 µM and 394.06 µM for rhenium aspirin and 228.6 µM and 1459.3 µM for rhenium indomethacin, respectively. At the same time, IC50 of aspirin and indomethacin were 10,024.42 µM and 3295.3 µM for Ishikawa, and 27,255.8 µM and 5489.3 µM for HEC-1A, respectively. Moreover, these derivatives were found to inhibit the proliferation of both cell lines in a time- and state-dependent manner. The Ishikawa cell proliferation was strongly inhibited by rhenium aspirin and rhenium indomethacin after 72-h incubation (*** = p < 0.001), while the HEC-1A proliferation was inhibited by the same agents already after 24-h incubation (*** = p < 0.001). Furthermore, the ROS level in the mitochondria of the tested cells generated in the presence of rhenium derivatives was higher than the original NSAIDs. That was associated with rhenium indomethacin exclusively, which had a significant effect (*** = p < 0.001) on both Ishikawa and HEC-1A cancer cells. Rhenium aspirin had a significant effect (*** = p < 0.001) on the mitochondrial ROS level of Ishikawa cells only. Overall, the research revealed a high potential of the rhenium derivatives of aspirin and indomethacin against endometrial cancer cells compared with the original NSAIDs.

Design of DNA Intercalators Based on 4-Carboranyl-1,8-Naphthalimides: Investigation of Their DNA-Binding Ability and Anticancer Activity.

In the present study, we continue our work related to the synthesis of 1,8-naphthalimide and carborane conjugates and the investigation of their anticancer activity and DNA-binding ability. For this purpose, a series of 4-carboranyl-1,8-naphthalimide derivatives, mitonafide, and pinafide analogs were synthesized using click chemistry, reductive amination, amidation, and Mitsunobu reactions. The calf thymus DNA (ct-DNA)-binding properties of the synthesized compounds were investigated by circular dichroism (CD), UV-vis spectroscopy, and thermal denaturation experiments. Conjugates 54-61 interacted very strongly with ct-DNA (∆Tm = 7.67-12.33 °C), suggesting their intercalation with DNA. They were also investigated for their in vitro effects on cytotoxicity, cell migration, cell death, cell cycle, and production of reactive oxygen species (ROS) in a HepG2 cancer cell line as well as inhibition of topoisomerase IIα activity (Topo II). The cytotoxicity of these eight conjugates was in the range of 3.12-30.87 µM, with the lowest IC50 value determined for compound 57. The analyses showed that most of the conjugates could induce cell cycle arrest in the G0/G1 phase, inhibit cell migration, and promote apoptosis. Two conjugates, namely 60 and 61, induced ROS production, which was proven by the increased level of 2'-deoxy-8-oxoguanosine in DNA. They were specifically located in lysosomes, and because of their excellent fluorescent properties, they could be easily detected within the cells. They were also found to be weak Topo II inhibitors.

Selection and validation of reference genes for qPCR in the human dermatophyte Trichophyton rubrum exposed to different carbon sources which promote adhesion-inducing conditions.

OBJECTIVE: The present study aimed to identify reference genes for qPCR analysis of T. rubrum growth in culture media which promote adhesion-inducing conditions to the host tissue. METHODS: We investigated the suitability of six candidate reference genes: ß-act, ß-tub, ef1-α, gapdh, sdha and rpl2 in reference strain of Trichophyton rubrum in response to different environmental stimuli. The stability of these genes was determined by NormFinder, geNorm and BestKeeper software. RESULTS: Our data obtained from the three algorithms revealed that mRNA expression levels of two candidate reference genes, ef1-α and ß-tub, remained the most stable in response to different carbon sources, while different sample sets had their own most stable reference genes, highlighting the importance of the choice of internal controls in qPCR experiments. We then checked the stability of ef1-α and ß-tub reference genes expression in different T. rubrum strains, suggesting that these two genes are reliable for normalisation of qPCR. Finally, we validated the suitability of selected reference genes as internal controls for target gene (SUB3) using the 2-ΔΔCt method. The best result indicating an increase of SUB3 transcript of T. rubrum was found when the two the most stable reference (ef1-α and ß-tub ) genes were used, as revealed by all three algorithms. CONCLUSIONS: We recommend the use of ef1-α and ß-tub as reference genes for qPCR analysis of target gene expression in T. rubrum exposed to different carbon sources which promote adhesion-inducing conditions.

A Digital Twin Approach for the Improvement of an Autonomous Mobile Robots (AMR's) Operating Environment-A Case Study.

The contemporary market creates a demand for continuous improvement of production, service, and management processes. Increasingly advanced IT technologies help designers to meet this demand, as they allow them to abandon classic design and design-testing methods in favor of techniques that do not require the use of real-life systems and thus significantly reduce the costs and time of implementing new solutions. This is particularly important when re-engineering production and logistics processes in existing production companies, where physical testing is often infeasible as it would require suspension of production for the testing period. In this article, we showed how the Digital Twin technology can be used to test the operating environment of an autonomous mobile robot (AMR). In particular, the concept of the Digital Twin was used to assess the correctness of the design assumptions adopted for the early phase of the implementation of an AMR vehicle in a company's production hall. This was done by testing and improving the case of a selected intralogistics task in a potentially "problematic" part of the shop floor with narrow communication routes. Three test scenarios were analyzed. The results confirmed that the use of digital twins could accelerate the implementation of automated intralogistics systems and reduce its costs.

Thiosemicarbazide Derivatives Decrease the ATPase Activity of Staphylococcus aureus Topoisomerase IV, Inhibit Mycobacterial Growth, and Affect Replication in Mycobacterium smegmatis.

Compounds targeting bacterial topoisomerases are of interest for the development of antibacterial agents. Our previous studies culminated in the synthesis and characterization of small-molecular weight thiosemicarbazides as the initial prototypes of a novel class of gyrase and topoisomerase IV inhibitors. To expand these findings with further details on the mode of action of the most potent compounds, enzymatic studies combined with a molecular docking approach were carried out, the results of which are presented herein. The biochemical assay for 1-(indol-2-oyl)-4-(4-nitrophenyl) thiosemicarbazide (4) and 4-benzoyl-1-(indol-2-oyl) thiosemicarbazide (7), showing strong inhibitory activity against Staphylococcus aureus topoisomerase IV, confirmed that these compounds reduce the ability of the ParE subunit to hydrolyze ATP rather than act by stabilizing the cleavage complex. Compound 7 showed better antibacterial activity than compound 4 against clinical strains of S. aureus and representatives of the Mycobacterium genus. In vivo studies using time-lapse microfluidic microscopy, which allowed for the monitoring of fluorescently labelled replisomes, revealed that compound 7 caused an extension of the replication process duration in Mycobacterium smegmatis, as well as the growth arrest of bacterial cells. Despite some similarities to the mechanism of action of novobiocin, these compounds show additional, unique properties, and can thus be considered a novel group of inhibitors of the ATPase activity of bacterial type IIA topoisomerases.

Design, Synthesis, and Evaluation of Novel 3-Carboranyl-1,8-Naphthalimide Derivatives as Potential Anticancer Agents.

We synthesized a series of novel 3-carboranyl-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, using click chemistry, reductive amination and amidation reactions and investigated their in vitro effects on cytotoxicity, cell death, cell cycle, and the production of reactive oxygen species in a HepG2 cancer cell line. The analyses showed that modified naphthalic anhydrides and naphthalimides bearing ortho- or meta-carboranes exhibited diversified activity. Naphthalimides were more cytotoxic than naphthalic anhydrides, with the highest IC50 value determined for compound 9 (3.10 µM). These compounds were capable of inducing cell cycle arrest at G0/G1 or G2M phase and promoting apoptosis, autophagy or ferroptosis. The most promising conjugate 35 caused strong apoptosis and induced ROS production, which was proven by the increased level of 2'-deoxy-8-oxoguanosine in DNA. The tested conjugates were found to be weak topoisomerase II inhibitors and classical DNA intercalators. Compounds 33, 34, and 36 fluorescently stained lysosomes in HepG2 cells. Additionally, we performed a similarity-based assessment of the property profile of the conjugates using the principal component analysis. The creation of an inhibitory profile and descriptor-based plane allowed forming a structure-activity landscape. Finally, a ligand-based comparative molecular field analysis was carried out to specify the (un)favorable structural modifications (pharmacophoric pattern) that are potentially important for the quantitative structure-activity relationship modeling of the carborane-naphthalimide conjugates.

Metallocenyl 7-ACA Conjugates: Antibacterial Activity Studies and Atomic-Resolution X-ray Crystal Structure with CTX-M ß-Lactamase.

The conjugation of organometallic groups to current ß-lactam antibiotics is a field of increasing study due to the ability of certain organometallic groups to enhance the antibiotic potency of these drugs. Herein, we report the antibacterial properties of two metallocenyl (ferrocenyl and ruthenocenyl) 7-aminocephalosporanic acid (7-ACA) antibiotic conjugates. Continuing a trend we found in our previous studies, the ruthenocenyl conjugate showed greater antibacterial activity than its ferrocenyl counterpart. Compared with the previously published 7-aminodesacetoxycephalosporanic acid (7-ADCA) conjugates, the 3-acetyloxymethyl group significantly improved the compounds' activity. Furthermore, the Rc-7-ACA compound was more active against clinical Staphylococcus aureus isolates than the ampicillin reference. Noticeably, neither of the two new compounds showed an undesirable toxic effect in HeLa and L929 cells at the concentrations at which they displayed strong antibacterial effects. The antibacterial activity of the two metallocenyl 7-ACA derivatives was further confirmed by scanning electron microscopy (SEM). SEM micrographs showed that bacteria treated with metallocenyl 7-ACA derivatives feature cell wall damage and morphology changes. Using a CTX-M-14 ß-lactamase competition assay based on nitrocefin hydrolysis, we showed that the Rc-7-ACA bound more favorably to CTX-M-14 than its ferrocenyl counterpart, again confirming the superiority of the ruthenocenyl moiety over the ferrocenyl one in interacting with proteins. We also report a 1.47 Å resolution crystal structure of Rc-7-ACA in complex with the CTX-M-14 E166A mutant, an enzyme sharing a similar active site configuration with penicillin-binding proteins, the molecular target of ß-lactam antibiotics. These results strengthen the case for the antibacterial utility of the Rc and Fc groups.

Synthesis and Evaluation of Biological Activities of Aziridine Derivatives of Urea and Thiourea.

In the present paper, we report the synthesis and evaluation of in vitro antimicrobial activities of aziridine-thiourea derivatives. A series of aziridines in reaction with isocyanates and isothiocyanates to obtain urea and thiourea derivatives were used. The structures of all new products were confirmed based on spectroscopic data (¹H-NMR, 13C-NMR, HR-MS). These compounds were screened for their in vitro antimicrobial activity against a panel of Gram-positive and Gram-negative strains of bacteria. Six of the tested compounds appeared to be promising agents against reference strains of Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis. Subsequently, compounds exhibiting promising antibacterial activity were tested against twelve clinical isolates of S. aureus from three different sources of infection. The most bactericidal compounds (MIC = 16-32 µg/mL) showed better antibacterial activity against MRSA than ampicillin and streptomycin. The in vitro cytotoxicity analysis on L929 murine fibroblast and HeLa human tumor cell line using the MTT assay allowed us to select the least toxic compounds for future investigation.

Biological evaluation and molecular modelling study of thiosemicarbazide derivatives as bacterial type IIA topoisomerases inhibitors.

In the present article, we describe the inhibitory potency of nine thiosemicarbazide derivatives against bacterial type IIA topoisomerases, their antibacterial profile and molecular modelling evaluation. We found that one of the tested compounds, compound 7, significantly inhibits activity of Staphylococcus aureus DNA gyrase with an IC(50) below 15 µM. Besides, this compound displays antibacterial activity on reference Staphylococuss spp. and Enterococcus faecalis strains as well as clinical S. aureus isolates at non-cytotoxic concentrations in mammalian cells with MIC values ranging from 16 to 32 µg/mL thereby indicating, in some cases, equipotent or even more effective action than standard drugs such as vancomycin, ampicillin and nitrofurantoin. The computational studies showed that both molecular geometry and the electron density distribution have a great impact on antibacterial activity of thiosemicarbazide derivatives.

Determination of the primary molecular target of 1,2,4-triazole-ciprofloxacin hybrids.

We have synthesized and examined the antibacterial activity, toxicity and affinity towards bacterial type II topoisomerases of a series of 1,2,4-triazole-ciprofloxacin hybrids. A number of these compounds displayed enhanced activity against Gram-positive and Gram-negative bacteria when compared to ciprofloxacin. The toxic concentrations of the obtained derivatives, evaluated on HEK-293 cells using MTT assay, were much higher than concentrations required to produce antibacterial effect. Finally, the results of enzymatic studies showed that the analyzed compounds demonstrated other preferences as regards primary and secondary molecular targets than ciprofloxacin.

1,4-Disubstituted thiosemicarbazide derivatives are potent inhibitors of Toxoplasma gondii proliferation.

A series of 4-arylthiosemicarbazides substituted at the N1 position with a 5-membered heteroaryl ring was synthesized and evaluated in vitro for T. gondii inhibition proliferation and host cell cytotoxicity. At non-toxic concentrations for the host cells all studied compounds displayed excellent anti-parasitic effects when compared to sulfadiazine, indicating a high selectivity of their anti-T. gondii activity. The differences in bioactivity investigated by DFT calculations suggest that the inhibitory activity of 4-aryl-thiosemicarbazides towards T. gondii proliferation is connected with the electronic structure of the molecule. Further, these compounds were tested as potential antibacterial agents. No growth-inhibiting effect on any of the test microorganisms was observed for all the compounds, even at high concentrations.

Application of microsatellite-primed PCR (MSP-PCR) and PCR melting profile (PCR-MP) method for intraspecies differentiation of dermatophytes.

In this study, two PCR-based methods (MSP-PCR and PCR-MP) were compared for their abilities to identify intraspecies variations of 23 isolates of Trichophyton rubrum, 78 isolates of Trichophyton interdigitale and 22 isolates of Microsporum canis, obtained mainly from patients in Lódz city. The results allowed to distinguish four types (containing two subtypes) characteristic for T. interdigitale and three types characteristic for T. rubrum using PCR-MP method. Analysis conducted using MSP-PCR with (GACA)4 primer revealed four types for T. rubrum and three types (containing one subtype) for T. interdigitale and with (GTG), primer showed two types (containing one subtype) for T. rubrum and six types (containing one subtype) for T. interdigitale. No differentiation was observed for the M. canis isolates with either method.

Evaluation of the antidermatophytic activity of potassium salts of N-acylhydrazinecarbodithioates and their aminotriazole-thione derivatives.

Nowadays, dermatophyte infections are relatively easy to cure, especially since the introduction of orally administered antifungals such as terbinafine and itraconazole. However, these drugs may cause side effects due to liver damage or their interactions with other therapeutics. Hence, the search for new effective chemotherapeutics showing antidermatophyte activity seems to be the urge of the moment. Potassium salts of N-acylhydrazinecarbodithioates are used commonly as precursors for the synthesis of biologically active compounds. Keeping that in mind, the activity of a series of five potassium N-acylhydrazinecarbodithioates (1a-e) and their aminotriazole-thione derivatives (2a-e) was evaluated against a set of pathogenic, keratinolytic fungi, such as Trichophyton ssp., Microsporum ssp. and Chrysosporium keratinophilum, but also against some Gram-positive and Gram-negative bacteria. All tested compounds were found non-toxic for L-929 and HeLa cells, with the IC30 and IC50 values assessed in the MTT assay above 128 mg/L. The compound 5-amino-3-(naphtalene-1-yl)-4,5-dihydro-1H-1,2,4-triazole-5-thione (2d) was found active against all fungal strains tested. Scanning Electron Microscopy (SEM) revealed inhibition of mycelium development of Trichophyton rubrum cultivated on nail fragments and treated with 2d 24 h after infection with fungal spores. Transmission Electron Microscopy (TEM) observation of mycelium treated with 2d showed ultrastructural changes in the morphology of germinated spores. Finally, the RNA-seq analysis indicated that a broad spectrum of genes responded to stress induced by the 2d compound. In conclusion, the results confirm the potential of N-acylhydrazinecarbodithioate derivatives for future use as promising leads for new antidermatophyte agents development.

[Bacterial biofilm as a cause of urinary tract infection--pathogens, methods of prevention and eradication]. / Biofilm bakteryjny jako przyczyna zakazen ukladu moczowego--mikroorganizmy patogenne, metody prewencji i eradykacji.

Urinary tract infections (UTI) are one of the common chronic and recurrent bacterial infections. Uropathogens which are able to form biofilm constitute a major etiological factor in UTI, especially among elder patients who are subject to long-term catheterization. It is caused by the capacity of the microorganisms for efficient and permanent colonization of tissues and also adhesion to diverse polymers used for urological catheter production such as propylene, polystyrene, silicone, polyvinyl chloride or silicone coated latex. Antibiotic therapy is the most common treatment for UTI. Fluoroquinolones, nitrofurans, beta-lactams, aminoglycosides, trimethoprim and sulfonamides are used predominantly. However, the biofilm due to its complex structure constitutes an effective barrier to the antibiotics used in the treatment of urinary tract infections. In addition, the growing number of multidrug resistant strains limits the usage of many of the currently available chemotherapeutic agents. Therefore, it seems important to search for new methods of treatment such as coating of catheters with non-pathogenic E. coli strains, the design of vaccines against fimbrial adhesive proteins of the bacterial cells or the use of bacteriophages.

Draft Genomes of Halophilic Chromohalobacter and Halomonas Strains Isolated from Brines of The Carpathian Foreland, Poland.

Chromohalobacter and Halomonas are genera of bacterial microorganisms belonging to the group of halophiles. They are characterized by high diversity and the ability to produce bioproducts of biotechnological importance, such as ectoine, biosurfactants and carotenoids. Here, we report three draft genomes of Chromohalobacter and two draft genomes of Halomonas isolated from brines. The length of the genomes ranged from 3.6 Mbp to 3.8 Mbp, and GC content was in the 60.11%-66.46% range. None of the analysed genomes has been assigned to any previously known species of the genus Chromohalobacter or Halomonas. Phylogenetic analysis revealed that Chromohalobacter 296-RDG and Chromohalobacter 48-RD10 belonged to the same species, and Chromohalobacter 11-W is more distantly related to the other two analysed strains than to Chromohalobacter canadensis. Halomonas strains 11-S5 and 25-S5 were clustered together and located close to Halomonas ventosae. Functional analysis revealed BGCs related to ectoine production in all genomes analysed. This study increases our overall understanding of halophilic bacteria and is also consistent with the notion that members of this group have significant potential as useful natural product producers.

Draft genomes of halophilic Archaea strains isolated from brines of the Carpathian Foreland, Poland.

Halophilic Archaea are a unique group of microorganisms living in saline environments. They constitute a complex group whose biodiversity has not been thoroughly studied. Here, we report three draft genomes of halophilic Archaea isolated from brines, representing the genera of Halorubrum, Halopenitus, and Haloarcula. Two of these strains, Boch-26 and POP-27, were identified as members of the genera Halorubrum and Halopenitus, respectively. However, they could not be assigned to any known species because of the excessive difference in genome sequences between these strains and any other described genomes. In contrast, the third strain, Boch-26, was identified as Haloarcula hispanica. Genome lengths of these isolates ranged from 2.7 Mbp to 3.0 Mbp, and GC content was in the 63.77%-68.77% range. Moreover, functional analysis revealed biosynthetic gene clusters (BGCs) related to terpenes production in all analysed genomes and one BGC for RRE (RiPP recognition element)-dependent RiPP (post-translationally modified peptides) biosynthesis. Moreover, the obtained results enhanced the knowledge about the salt mines microbiota biodiversity as a poorly explored environment so far.

Acridine/Acridone-Carborane Conjugates as Strong DNA-Binding Agents with Anticancer Potential.

Synthesis of acridine derivatives that act as DNA-targeting anticancer agents is an evolving field and has resulted in the introduction of several drugs into clinical trials. Carboranes can be of importance in designing biologically active compounds due to their specific properties. Therefore, a series of novel acridine analogs modified with carborane clusters were synthesized. The DNA-binding ability of these analogs was evaluated on calf thymus DNA (ct-DNA). Results of these analyses showed that 9-[(1,7-dicarba-closo-dodecaborane-1-yl)propylamino]acridine (30) interacted strongly with ct-DNA, indicating its ability to intercalate into DNA, whereas 9-[(1,7-dicarba-closo-dodecaborane-1-yl)propanamido]acridine (29) changed the B-form of ct-DNA to the Z form. Compound 30 demonstrated cytotoxicity, was able to inhibit cell proliferation, arrest the cell cycle in the S phase in the HeLa cancer cell line, and induced the production of reactive oxygen species (ROS). In addition, it was specifically localized in lysosomes and was a weak inhibitor of Topo IIα.