Rational design and synthesis of triazene-amonafide derivatives as novel potential antitumor agents causing oxidative damage towards DNA through intercalation mode.

In this work, we rationally designed and synthesized two novel triazene-amonafide derivatives 2-(2-(diisopropylamino)ethyl)-5-(3,3-dimethyltriaz-1-en-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-11) and 5-(3,3-diethyltriaz-1-en-1-yl)-2-(2-(diisopropylamino)ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-12) as potential antitumor agents. The DNA damage induced by the intercalation mode of D-11 (D-12) towards DNA was electrochemically detected through the construction of efficient biosensors. The consecutive processes of reversible redox of naphthylimide ring and irreversible oxidation of triazene moiety were elucidated on the surface of glassy carbon electrode (GCE) by CV, SWV, and DPV methods. Electrochemical biosensors were obtained through the immobilization of ctDNA, G-quadruplexes, poly(dG), and poly(dA), respectively, on the clean surface of GCE. After the incubation of biosensors with D-11 or D-12, the peaks of dGuo and dAdo decreased prominently, and the peak of 8-oxoGua appeared at +0.50 V, suggesting that the interaction between D-11 (D-12) and DNA could result in the oxidative damage of guanine. Unexpected, the as-prepared DNA biosensor possessed satisfactory anti-interference property and good practicability in real samples. UV-vis and fluorescence spectra, and gel electrophoresis assays were employed to further confirm the intercalation mode of D-11 (D-12) towards DNA base pairs. Moreover, D-11 was proved to exhibit stronger anti-proliferation activity than mitionafide and amonafide against both A549 and HeLa cell lines.

In vitro multitarget activity of sulfadiazine substituted triazenes as antimicrobial, cytotoxic, and larvicidal agents.

Multidrug resistance (MDR) causes difficulties in the treatment of infections and cancer. Research and development studies have become increasingly important for the strategy of preventing MDR. There is a need for new multitarget drug research and advancement to reduce the development of drug resistance in drug-drug interactions and reduce cost and toxic effects. This study aimed to determine the effects of multi-target triazene compounds on antibacterial, antifungal, antiviral, cytotoxic, and larvicidal activities were investigated in vitro. A series of 12 novel of 1,3-diaryltriazene-substituted sulfadiazine (SDZ) derivatives were synthesized, and the obtained pure products characterized in detail by spectroscopic and analytic methods (FT-IR, 1 H-NMR, 13 C-NMR, and melting points). The antibacterial and antifungal activities of these derivatives (AH1-12) were determined by broth microdilution method. All derivatives have been evaluated in cell-based assays for cytotoxic and antiviral activities against Modified Vaccinia Virus Ankara. The larvicidal efficacy of these chemical compounds was also investigated by using Lucilia sericata (L. sericata) larvae. Twelve 1,3-diaryltriazene-substituted SDZ derivatives (AH1-12) were designed and developed as potent multitargeted compounds. Among them, the AH1 derivative showed the most antibacterial and antifungal activity. Besides, synthesized derivatives AH2, AH3, AH5, and AH7 showed higher antiviral activity than SDZ. All synthesized derivatives showed higher cytotoxic activity than SDZ. Also, they showed larvicidal activity at 72 h of the experiment. As a result, these compounds might be great leads for the development of next-generation multitargeted agents.

Synthesis and Reactivity of a Terminal 1-Alkynyl Triazene.

1-Alkynyl triazenes are versatile reagents in synthetic organic chemistry, but the structural diversity of this compound class has so far been limited. Herein, we describe the synthesis of a terminal 1-alkynyl triazene. Subsequent functionalization allows the preparation of 1-alkynyl triazenes with a range of functional groups including esters, alcohols, cyanides, phosphonates, and amides. Furthermore, the terminal 1-alkynyl triazene can be used for the synthesis of di- and triynes and for the preparation of (hetero)aromatic triazenes in metal-catalyzed cyclization reactions.

Anions Containing Tripoid Conjugated N4- System: Salts of 5-(Substituted Amino)-[1,2,3]triazolo[4,5-c][1,2,5]oxadiazol-5-ium-4-ides, as well as Their Synthesis, Structure, and Thermal Stability.

A strategy for the synthesis of 5-((2-cyanoethyl)-X-amino)-[1,2,3]triazolo[4,5-c][1,2,5]oxadiazol-5-ium-4-ides (X = H; CH2CH2CN; NO2 (4a); CN (4b); CO2Et (4c)) starting from 3-amino-4-azido-1,2,5-oxadiazole was developed. The key step in this strategy is the intramolecular thermolytic cyclization of the azido group and the bis(2-cyanoethyl)triazene group. Removal of the 2-cyanoethyl protecting group from amides 4a-c gave potassium salt of the corresponding nitramide and sodium salts of cyano- and ethoxycarbonylamide. The structure and thermal stability of the synthesized compounds were studied experimentally using multinuclear NMR spectroscopy, X-ray crystallography, thermogravimetry, and differential scanning calorimetry.

CeO2-Decorated Metal-Organic Framework for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) is quickly developing as a hopeful cancer treatment. However, hypoxic tumors, poor targeting, and photosensitizers (PS) aggregation limited the efficiency of PDT. Here, we report a hyaluronic acid (HA)-modified CeO2-nanoparticle-decorated metal-organic framework (PCN-224@CeO2-HA) to enhance PDT and achieve targeted treatment. CeO2 catalyzes H2O2 to produce O2 to solve hypoxia problems. HA could target the CD44 receptor, which is highly expressed on the tumor cell membranes. The growth of tumor cells 4T1 and MCF-7 was controlled distinctly after being incubated with PCN-224@CeO2-HA under laser irradiation, while the survival ability of normal cell LO2 was nearly unchanged. Importantly, PCN-224@CeO2-HA could be effectively aggregated within the tumor area after 12 h of injection, and the tumor growth was remarkably inhibited under laser irradiation. PCN-224@CeO2-HA presented good biocompatibility and an excellent antitumor effect, providing a new strategy to produce O2 in situ for enhanced PDT.

Substitution of α-Azido Sulfones with Thiolates to Form α-Azido Sulfides.

Upon treatment of α-azido sulfones with a thiol in the presence of 1,1,3,3-tetramethylguanidine, substitution of the sulfonyl group with a thiolate occurred, resulting in the formation of α-azido sulfides. Based on experimental results and DFT calculations, a reaction mechanism that involves the addition of a thiolate to the azido group and generation of an alkylidene triazene is proposed.

MMP-2 Inhibitor-Mediated Tumor Microenvironment Regulation Using a Sequentially Released Bio-Nanosystem for Enhanced Cancer Photo-Immunotherapy.

Combining photodynamic therapy (PDT) with natural killer (NK) cell-based immunotherapy has shown great potential against cancers, but the shedding of NK group 2, member D ligands (NKG2DLs) on tumor cells inhibited NK cell activation in the tumor microenvironment. Herein, we assembled microenvironment-/light-responsive bio-nanosystems (MLRNs) consisting of SB-3CT-containing ß-cyclodextrins (ß-CDs) and photosensitizer-loaded liposomes, in which SB-3CT was considered to remodel the tumor microenvironment. ß-CDs and liposomes were linked by metalloproteinase 2 (MMP-2) responsive peptides, enabling sequential release of SB-3CT and chlorin e6 triggered by the MMP-2-abundant tumor microenvironment and 660 nm laser irradiation, respectively. Released SB-3CT blocked tumor immune escape by antagonizing MMP-2 and promoting the NKG2D/NKG2DL pathway, while liposomes were taken up by tumor cells for PDT. MLRN-mediated photo-immunotherapy significantly induced melanoma cell cytotoxicity (83.31%), inhibited tumor growth (relative tumor proliferation rate: 1.13% of that of normal saline) in the xenografted tumor model, and enhanced tumor-infiltrating NK cell (148 times) and NKG2DL expression (9.55 and 16.52 times for MICA and ULBP-1, respectively), achieving a synergistic effect. This study not only provided a simple insight into the development of new nanomedicine for programed release of antitumor drugs and better integration of PDT and immunotherapy but also a novel modality for clinical NK cell-mediated immunotherapy against melanoma.

Synthesis of dual-stimuli responsive metal organic framework-coated iridium oxide nanocomposite functionalized with tumor targeting albumin-folate for synergistic photodynamic/photothermal cancer therapy.

The synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted considerable attention in the field of cancer therapy because of its excellent anti-tumor effect. This work provides a novel pH/NIR responsive therapeutic nanoplatform, IrO2@ZIF-8/BSA-FA (Ce6), producing a synergistic effect of PTT-PDT in the treatment of osteosarcoma. Iridium dioxide nanoparticles (IrO2 NPs) with exceptional catalase-like activity and PTT effects were synthesized by a hydrolysis method and decorated with zeolitic imidazolate framework-8 (ZIF-8) shell layer to promote the physical absorption of Chlorin e6 (Ce6), and further functionalized with bovine serum albumin-folate acid (BSA-FA) for targeting tumor cells. The IrO2@ZIF-8/BSA-FA nanocomposite indicated an outstanding photothermal heating conversion efficiency of 62.1% upon laser irradiation. In addition, the Ce6 loading endows nanoplatform with the capability to induce cell apoptosis under 660 nm near-infrared (NIR) laser irradiation through a reactive oxygen species (ROS)-mediated mechanism. It was further testified that IrO2@ZIF-8/BSA-FA can function as a catalase and convert the endogenous hydrogen peroxide (H2O2) into oxygen (O2) to improve the local oxygen pressure under the acidic tumor microenvironment (TME), which could subsequently amplified PDT-mediated ROS cell-killing performance via relieving hypoxia microenvironment of tumor. Both in vitro and in vivo experimental results indicated that the nanomaterials were good biocompatibility, and could remarkably achieve tumor-specific and enhanced combination therapy outcomes as compared with the corresponding PTT or PDT monotherapy. Taken together, this work holds great potential to design an intelligent multifunctional therapeutic nanoplatform for cancer therapy.

Surfactant-Free Green Synthesis of Au@Chlorophyll Nanorods for NIR PDT-Elicited CDT in Bladder Cancer Therapy.

The facile and straightforward fabrication of NIR-responsive theranostic materials with high biocompatibility is still an unmet need for nanomedicine applications. Here, we used a natural photosensitizer, iron chlorophyll (Chl/Fe), for the J-aggregate template-assisted synthesis of Au@Chl/Fe nanorods with high stability. The assembly of a high amount of Chl/Fe J-aggregate onto the Au surface enabled red-NIR fluorescence for monitoring and tracking residential tumor lesions. The Chl/Fe moieties condensed on the nanorods could change the redox balance by the photon induction of reactive oxygen species and attenuate iron-mediated lipid peroxidation by inducing a Fenton-like reaction. After conjugation with carboxyphenylboronic acid (CPBA) to target the glycoprotein receptor on T24 bladder cancer (BC) cells, the enhanced delivery of Au@Chl/Fe-CPBA nanorods could induce over 85% cell death at extremely low concentrations of 0.16 ppm[Au] at 660 nm and 1.6 ppm[Au] at 785 nm. High lipid peroxidation, as shown by BODIPY staining and GSH depletion, was observed when treated T24 cells were exposed to laser irradiation, suggesting that preliminary photodynamic therapy (PDT) can revitalize Fenton-like reaction-mediated chemodynamic ferroptosis in T24 cells. We also manipulated the localized administration of Au@Chl-Fe combined with PDT at restricted regions in orthotopic tumor-bearing mice to cure malignant BC successfully without recurrence. By intravesical instillation of the Au@Chl/Fe-CPBA nanorods, this localized treatment could prevent the material from entering the systemic circulation, thus minimizing systemic toxicity. Upon activating NIR-PDT-elicited chemodynamic therapy, ultrasound imaging revealed almost complete tumor remission. Anti-tumor efficacy and survival benefit were achieved with a green photosensitizer.

Dual-responsive nano-prodrug micelles for MRI-guided tumor PDT and immune synergistic therapy.

Micelles as nanocarriers not only offer new opportunities for early diagnosis and treatment of malignant cancers but also encounter numerous barriers in the path of efficient delivery of drugs to diseased areas in the body. To address these issues, we developed a pH/GSH responsive nano-prodrug micelle (NLG919/PGA-Cys-PPA@Gd) with a high drug-loading ratio and controlled drug release performance for MRI-guided tumor photodynamic therapy (PDT) and immune synergistic therapy. Under normal conditions, theranostic nanomicelles remained stable and in a photo-quenched state. Upon accumulation in the tumor site, however, the micelles demonstrated tumor microenvironment (TME) triggered photoactive formed-PPA (a photosensitizer) and NLG919 (an indoleamine 2,3-dioxygenase (IDO) inhibitor) release because the amide bonds of PGA-Cys-PPA and the disulfide linkage of Cys were sensitive to pH and GSH, respectively. More importantly, these micelles could avoid the undesired PPA leakage in blood circulation due to the conjugation between PPA and polymers. Furthermore, the obtained micelles could also enhance the contrast of T1-weighted MRI of tumors by virtue of their high relaxivity (r1 = 29.85 mM-1 s-1). In vitro and in vivo results illustrated that the micelles had good biocompatibility and biosafety. On the basis of the efficient drug delivery strategies in PDT and IDO pathway inhibition, this intelligent dual-drug delivery system could serve as an effective approach for MRI guided combination therapy of cancer.

Acceptor Planarization and Donor Rotation: A Facile Strategy for Realizing Synergistic Cancer Phototherapy via Type I PDT and PTT.

Tumor hypoxia seriously impairs the therapeutic outcomes of type II photodynamic therapy (PDT), which is highly dependent upon tissue oxygen concentration. Herein, a facile strategy of acceptor planarization and donor rotation is proposed to design type I photosensitizers (PSs) and photothermal reagents. Acceptor planarization can not only enforce intramolecular charge transfer to redshift NIR absorption but also transfer the type of PSs from type II to type I photochemical pathways. Donor rotation optimizes photothermal conversion efficiency (PCE). Accordingly, three 3,6-divinyl-substituted diketopyrrolopyrrole (DPP) derivatives, 2TPAVDPP, TPATPEVDPP, and 2TPEVDPP, with different number of rotors were prepared. Experimental results showed that three compounds were excellent type I PSs, and the corresponding 2TPEVDPP nanoparticles (NPs) with the most rotors possessed the highest PCE. The photophysical properties of 2TPEVDPP NPs are particularly suitable for in vivo NIR fluorescence imaging-guided synergistic PDT/PTT therapy. The proposed strategy is helpful for exploiting type I phototherapeutic reagents with high efficacy for synergistic PDT and PTT.

Photodynamic Therapy-Induced Cyclooxygenase 2 Expression in Tumor-Draining Lymph Nodes Regulates B-Cell Expression of Interleukin 17 and Neutrophil Infiltration.

Photodynamic therapy (PDT) is an effective anticancer modality approved by the U.S. Food and Drug Administration (FDA). Antitumor immunity can be augmented during PDT by inducing sterile inflammation in an acute manner, and this process is characterized by interleukin 17 (IL-17)-mediated neutrophil infiltration to tumor-draining lymph nodes (TDLNs). However, the inflammatory factors that influence IL-17 expression in TDLNs are poorly understood. Prior studies have linked the cyclooxygenase 2 (COX2)-driven prostaglandin E2 (PGE2) pathway to IL-17 expression. Here, we report that an immune-activating PDT regimen (imPDT) induces COX2/PGE2 expression in TDLNs, whereby IL-17 expression is facilitated without corresponding effects on the expression of RORγt, the transcriptional driver of the canonical IL-17 pathway. Pharmacologic inhibition with NS398, a COX2 inhibitor, was utilized to demonstrate that imPDT-induced COX2 regulates RORγt-independent expression of IL-17 by B cells and neutrophil entry into TDLNs. Depletion of B cells prior to imPDT significantly reduced neutrophil entry into TDLNs following treatment, and diminishes the efficacy of imPDT, which is dependent upon antitumor immunity. These findings are suggestive of a novel role for B cells in the augmentation of antitumor immunity by imPDT.

Diaryl triazenes inhibit cytochrome P450 1A1 and 1B1 more strongly than aryl morpholino triazenes.

Several diaryl triazene derivatives were synthesized and tested for their ability to inhibit cytochrome P450 1A1 and 1B1 as a potential means to prevent and treat cancer. These compounds are more planar than their conformational flexible aryl morpholino triazene counterparts that were previously shown to inhibit the above enzymes. As a result, the diaryl triazenes are more likely to exhibit increased binding to the enzyme active sites and inhibit these enzymes more strongly than the aryl morpholino triazenes. The data indicates that the diaryl triazenes inhibit cytochrome P450 1A1 and 1B1 one to two orders of magnitude more strongly than the aryl morpholino triazenes. Furthermore, compounds 8-10 strongly inhibited cytochrome P450 1B1 with IC50 values of 51 nM, 740 nM, and 590 nM respectively. Thus, diaryl triazenes should be further investigated as a potential chemopreventive agent.

Biosynthesis of triacsin featuring an N-hydroxytriazene pharmacophore.

Triacsins are an intriguing class of specialized metabolites possessing a conserved N-hydroxytriazene moiety not found in any other known natural products. Triacsins are notable as potent acyl-CoA synthetase inhibitors in lipid metabolism, yet their biosynthesis has remained elusive. Through extensive mutagenesis and biochemical studies, we here report all enzymes required to construct and install the N-hydroxytriazene pharmacophore of triacsins. Two distinct ATP-dependent enzymes were revealed to catalyze the two consecutive N-N bond formation reactions, including a glycine-utilizing, hydrazine-forming enzyme (Tri28) and a nitrite-utilizing, N-nitrosating enzyme (Tri17). This study paves the way for future mechanistic interrogation and biocatalytic application of enzymes for N-N bond formation.

PDT with genetically encoded photosensitizer miniSOG on a tumor spheroid model: A comparative study of continuous-wave and pulsed irradiation.

BACKGROUND: Therapeutic effects of PDT depend on many factors, including the amount of singlet oxygen, localization of photosensitizer and irradiation protocol. The present study was aimed to compare the cytotoxic mechanisms of PDT under continuous-wave (CW) and pulsed irradiation using a tumor spheroid model and a genetically encoded photosensitizer miniSOG. METHODS: 1O2 detection in miniSOG and flavin mononucleotide (FMN) solutions was performed. Photobleaching of miniSOG in solution and in HeLa tumor spheroids was analyzed. Tumor spheroid morphology and growth and the cell death mechanisms after PDT in CW and pulsed modes were assessed. RESULTS: We found a more rapid 1O2 generation and a higher photobleaching rate in miniSOG solution upon irradiation in pulsed mode compared to CW mode. Photobleaching of miniSOG in tumor spheroids was also higher after irradiation in the pulsed mode. PDT of spheroids in CW mode resulted in a moderate expansion of the necrotic core of tumor spheroids and a slight inhibition of spheroid growth. The pulsed mode was more effective in induction of cell death, including apoptosis, and suppression of spheroid growth. CONCLUSIONS: Comparison of CW and pulsed irradiation modes in PDT with miniSOG showed more pronounced cytotoxic effects of the pulsed mode. Our results suggest that the pulsed irradiation regimen enables enhanced 1O2 production by photosensitizer and stimulates apoptosis. GENERAL SIGNIFICANCE: Our results provide more insights into the cellular mechanisms of anti-cancer PDT and open the way to improvement of light irradiation protocols.

Short Chain Fatty Acid Acetate Increases TNFα-Induced MCP-1 Production in Monocytic Cells via ACSL1/MAPK/NF-κB Axis.

Short-chain fatty acid (SCFA) acetate, a byproduct of dietary fiber metabolism by gut bacteria, has multiple immunomodulatory functions. The anti-inflammatory role of acetate is well documented; however, its effect on monocyte chemoattractant protein-1 (MCP-1) production is unknown. Similarly, the comparative effect of SCFA on MCP-1 expression in monocytes and macrophages remains unclear. We investigated whether acetate modulates TNFα-mediated MCP-1/CCL2 production in monocytes/macrophages and, if so, by which mechanism(s). Monocytic cells were exposed to acetate with/without TNFα for 24 h, and MCP-1 expression was measured. Monocytes treated with acetate in combination with TNFα resulted in significantly greater MCP-1 production compared to TNFα treatment alone, indicating a synergistic effect. On the contrary, treatment with acetate in combination with TNFα suppressed MCP-1 production in macrophages. The synergistic upregulation of MCP-1 was mediated through the activation of long-chain fatty acyl-CoA synthetase 1 (ACSL1). However, the inhibition of other bioactive lipid enzymes [carnitine palmitoyltransferase I (CPT I) or serine palmitoyltransferase (SPT)] did not affect this synergy. Moreover, MCP-1 expression was significantly reduced by the inhibition of p38 MAPK, ERK1/2, and NF-κB signaling. The inhibition of ACSL1 attenuated the acetate/TNFα-mediated phosphorylation of p38 MAPK, ERK1/2, and NF-κB. Increased NF-κB/AP-1 activity, resulting from acetate/TNFα co-stimulation, was decreased by ACSL1 inhibition. In conclusion, this study demonstrates the proinflammatory effects of acetate on TNF-α-mediated MCP-1 production via the ACSL1/MAPK/NF-κB axis in monocytic cells, while a paradoxical effect was observed in THP-1-derived macrophages.

ALA-PDT successfully treated Majocchi's granuloma by directly killing Trichophyton tonsurans and recruiting T lymphocytes.

BACKGROUND: Majocchi's granuloma (MG) is a deep persistent suppurative granulomatous perifolliculitis which might be caused by Trichophyton tonsurans (T. tonsurans). Conventional treatment for MG is oral administration of systematic antifungal drugs, associated with a low cure rate and a high relapse rate. ALA-PDT is a new approach for fungal infection. METHODS: A case of refractory MG was treated by 3 times of ALA-PDT. At the same time, T. tonsurans strains isolated from the lesions of the patient were used for an in vitro inhibition experiment and an in vivo experiment in guinea pig model to furtherly verify the effectiveness and investigate the mechanism of ALA-PDT for T. tonsurans. RESULTS: After 3 times of ALA-PDT, the lesions of MG were eliminated. And the mycological and pathological examination showed a disappearance of fungi in follicles. In vitro and in vivo experiment both demonstrated that ALA-PDT could obviously inhibit the growth of T. tonsurans partly by directly destroying the structure of fungal cells and recruiting CD4 + T cells. CONCLUSION: ALA-PDT is a potentially effective noninvasive method for the treatment of MG with mechanisms of direct killing and with CD4+ T cell-mediated immune response.

Enhanced lipid metabolism induces the sensitivity of dormant cancer cells to 5-aminolevulinic acid-based photodynamic therapy.

Cancer can develop into a recurrent metastatic disease with latency periods of years to decades. Dormant cancer cells, which represent a major cause of recurrent cancer, are relatively insensitive to most chemotherapeutic drugs and radiation. We previously demonstrated that cancer cells exhibited dormancy in a cell density-dependent manner. Dormant cancer cells exhibited increased porphyrin metabolism and sensitivity to 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). However, the metabolic changes in dormant cancer cells or the factors that enhance porphyrin metabolism have not been fully clarified. In this study, we revealed that lipid metabolism was increased in dormant cancer cells, leading to ALA-PDT sensitivity. We performed microarray analysis in non-dormant and dormant cancer cells and revealed that lipid metabolism was remarkably enhanced in dormant cancer cells. In addition, triacsin C, a potent inhibitor of acyl-CoA synthetases (ACSs), reduced protoporphyrin IX (PpIX) accumulation and decreased ALA-PDT sensitivity. We demonstrated that lipid metabolism including ACS expression was positively associated with PpIX accumulation. This research suggested that the enhancement of lipid metabolism in cancer cells induces PpIX accumulation and ALA-PDT sensitivity.

The assessment of psychology, quality of life in acne patients and evaluation of ALA-PDT for moderate to severe acne.

OBJECTIVE: To evaluate the state of psychology and quality of life of patients effected by acne and also the efficacy and safety of photodynamic therapy with topical 5-aminolevulinic acid (ALA-PDT) for moderate to severe acne patients. METHODS: In the questionnaire part, a pre-designed form was filled out. The questionnaire was comprised of 2 sections related to acne including sociodemographic and disease information as well as Cardiff Acne Disability Index (CADI) and Self-Rating Anxiety Scale (SAS). In the trial part, the ALA-PDT was applied to moderate to severe acne patients. Fresh 5% ALA solution was topically applied to face or face & neck. After 1 h's incubation, a LED device was illuminated. A power density of 60-100 mW/cm2 was delivered for 20 min. All the patients finished 3-4 sessions of ALA-PDT at 7-10 days intervals. Non-invasive detections were taken for skin moisture, oil, and VISIA indexes. Adverse events were recorded during and after the treatment. RESULTS: A total of 247 acne patients finished questionnaires. Over 97 % patients were assessed as mild to severe impacts in CADI questionnaire and 37.6 % patients had various degrees of anxiety in SAS questionnaire. The higher the BMI was, the higher the CADI points were (G = 0.278, p = 0.005). The severity of acne was correlated with psychology and quality of life (CADI: G = 0.367, p = 0.000; SAS: G = 0.285, p = 0.003). A total of 116 patients with moderate or severe acne accepted ALA-PDT and completed at least 3 sessions (PDT3) or even PDT4. After 1 session of treatment (AT1) and AT2, the efficiencies of all patients were 5.2 % and 29.3 %. For patients with PDT3, the efficiencies at follow-up at 1st month after last session (FU1), FU2 and FU3 were 59.4 %, 66.7 % and 78.3 %, respectively. For patients with PDT4, the efficiencies at AT3 and FU1-3 were 51.3 %, 63.6 %, 76.5 % and 85.7 %, respectively. The efficacies of PDT4 patients showed an increasing trend from FU1 to FU3 (G = 0.480, p = 0.004). Acne lesions of mild to severe were correlated with the treatment efficacies (FU1: G = 0.354, p = 0.000; FU2: G = 0.474, p = 0.000; FU3: G = 0.397, p = 0.000). Nearly 15 % patients were followed up for 12 months and among them 52.9 % patients were able to maintain ≥90 % improvement rate. There were no statistically significant differences before and after treatment (p > 0.05) according to the skin moisture content, oil content, ultraviolet ray spots, brown spots, red areas, and purple textures measured. The adverse reactions of ALA-PDT, including local burning sensation, mild pain sensation, mild edema erythema, reactive acne, pigmentation, etc., were temporary and tolerable. CONCLUSION: In our study, 97.2 % patients were rated as impact in CADI questionnaire and 37.6 % patients had anxiety in SAS questionnaire. It is necessary to control weight and disease progression. The efficiencies of ALA-PDT for moderate and severe acne were 59.4%-85.7% at follow-ups of 1st, 2nd or 3rd month after last session. The adverse reactions of ALA-PDT were temporary and tolerable.

Assessment of the biological potential of diaryltriazene-derived triazene compounds.

In the present study, novel, 1,3-diaryltriazene-derived triazene compounds were synthesized and tested. Triazenes are versatile and belong to a group of alkylating agents with interesting physicochemical properties and proven biological activities. This study describes the synthesis, molecular and crystalline structure, biological activity evaluation, and antifungal and antimicrobial potentials of 1,3-bis(X-methoxy-Y-nitrophenyl)triazenes [X = 2 and 5; Y = 4 and 5]. The antimicrobial and antifungal activities of the compounds were tested by evaluating the sensitivity of bacteria (American Type Culture Collection, ATCC) and clinical isolates to their solutions using standardized microbiological assays, cytotoxicity evaluation, and ecotoxicity tests. The antimicrobial potentials of triazenes were determined according to their minimum inhibitory concentrations (MICs); these compounds were active against gram-positive and gram-negative bacteria, with low MIC values. The most surprising result was obtained for T3 having the effective MIC of 9.937 µg/mL and antifungal activity against Candida albicans ATCC 90028, C. parapsilosis ATCC 22019, and C. tropicallis IC. To the best of our knowledge, this study is the first to report promising activities of triazene compounds against yeast and filamentous fungi. The results showed the potential utility of triazenes as agents affecting selected resistant bacterial and fungal strains.