Triazole Ring Research Articles

Novel quinazoline-1,2,3-triazole hybrids with anticancer and MET kinase targeting properties

Oncogenic activation of receptor tyrosine kinases (RTKs) such as MET is associated with cancer initiation and progression. We designed and synthesized a new series of quinazoline derivatives bearing 1,2,3-triazole moiety as targeted anticancer agents. The MET inhibitory effect of synthesized compounds was assessed by homogeneous time-resolved fluorescence (HTRF) assay and western blot analysis. Sulforhodamine B assay was conducted to examine the antiproliferative effects of synthetic compounds against 6 cancer cell lines from different origins including MET-dependent AsPC-1, EBC-1 and MKN-45 cells and also Mia-Paca-2, HT-29 and K562 cells. The growth inhibitory effect of compounds in a three-dimensional spheroid culture was examined by acid phosphatase (APH) assay, while apoptosis induction was evaluated by Annexin V/propidium iodide method. Compound 8c bearing p-methyl benzyl moiety on the triazole ring exhibited the highest MET inhibitory capacity among tested agents that was further confirmed by western blot findings. Derivatives 8c and 8h exhibited considerable antiproliferative effects against all tested cell lines, with more inhibitory effects against MET-positive cells with IC50 values as low as 6.1 μM. These two agents also significantly suppressed cell growth in spheroid cultures and induced apoptosis in MET overexpressing AsPC-1 cells. Moreover, among a panel of 24 major oncogenic kinases, the PDGFRA kinase was identified as a target of 8c and 8h compounds. The docking study results of compounds 8c and 8h were in agreement with experimental findings. The results of the present study suggest that quinazoline derivatives bearing 1,2,3-triazole moiety may represent promising targeted anticancer agents.

Novel hybrid motifs of 4-nitroimidazole-piperazinyl tagged 1,2,3-triazoles: Synthesis, crystal structure, anticancer evaluations, and molecular docking study

4-((4-(1-benzyl-2-methyl-4-nitro-1H-imidazole-5-yl)piperazine-1-yl)methyl)-1-substituted-1H-1,2,3-triazole motifs are designed and synthesized via click chemistry. The reaction of 1-(N1-benzyl- 2-methyl-4-nitro-1H-imidazole- 5-yl)-4-(prop-2-yn-1-yl) piperazine 5 as new scaffold with diverse primary azides to selectively produce 1,4-disubstituted-1,2,3-triazoles 9a–k, 10a–c and 11a–q. Physicochemical methods: when 1H NMR, 13C NMR, and HRMS are utilized to fully characterize all synthesized compounds. X-ray structural determination and analysis for compound 9a is also performed. The newly designed chromophores are assessed for their anti-proliferative potency against three selected human cancer cell lines (MCF-7, HepG2, and PC3), and one normal cell line (Dermal/Fibroblast). Compounds 9g and 9k have shown potent activities against the MCF-7 cell line with IC50 values of (2.00 ± 0.03 μM) and (5.00 ± 0.01 μM) respectively. ADMET studies and Molecular docking investigations are performed on the most active hybrid nitroimidazole derivatives 9g and 9k with 4-hydroxytamoxifen (4-OHT) at the human estrogen receptor alpha (hER) during binding active sites to study the ligand–protein interactions and free binding energies at atomic levels. The triazole ring in the 9g derivative forms a hydrogen bond with Asp58 with distance 3.2 Å. And it is found that polar contact with His231 amino acid residue.In silico assessment of the compounds showed very good pharmacokinetic properties based on their physicochemical values, also the ADMET criteria of the most active hybrid systems are within the acceptable range.

Crystal structure of 2-{[5-(methyl-sulfan-yl)-4-phenyl-4H-1,2,4-triazol-3-yl]meth-yl}benzo[d]thia-zole.

In the structure of the title compound, C17H14N4O2, the triazole ring exhibits inter-planar angles of 63.86 (2) and 76.96 (2)° with the phenyl and benzo-thia-zole planes, respectively. The C-C-C angle at the methyl-ene group is rather wide at 114.28 (4)°. The packing involves three borderline C-H⋯N contacts, two of which combine to form layers parallel to ac, and a pairing of the triazole rings across an inversion centre [inter-planar distance of 3.1852 (2) Å].

Inserting urethane into 1,2,3‐triazole click‐cured solid propellant binder to form microphase separation and enhance mechanical and combustible performances

AbstractHuisgen‐click curing systems are widely used in solid propellant binders due to their low humidity sensitivity and mild reaction conditions. However, the rigid triazole rings from the Huisgen‐click reaction decrease the molecular moving ability and increase decomposition temperature, lowering the mechanical and combustion performance. Thus, we bonded the Huisgen‐click system and polyester binders with urethane, forming microphase separation and improving chemical stability. The results show that the elongation at break, tensile strength, and Young's modulus of the binders increase by 533.3%, 201.2%, and 1263.9%, respectively. Furthermore, the urethane reduces the thermal resistance index of the binders from 191.2 to 179.2°C, which means better combustion performance. Further mechanism study reveals that the urethane leads to microphase separation, which aggregates the hard segments and weakens their restriction effect on the molecular motion of polyether. Such a microphase separation brings comprehensive improvement in the mechanical properties of the solid propellants and probably can be used in other multi‐component systems of energetic materials.

Interpenetration Phenomena via Anion Template Effects in Fe(II) and Co(II) Coordination Networks with a Bis-(1,2,4-triazole) Ligand.

Seven new coordination networks, [Fe(tbbt)3](BF4)2 (1), [Co(tbbt)3](BF4)2 (2), [Fe(tbbt)3](ClO4)2 (3), [Co(tbbt)3](ClO4)2 (4), [Fe(NCS)2(tbbt)2] (5), [Co(NCS)2(tbbt)2] (6), and [Fe(H2O)2(tbbt)2]Br2·2H2O (7), were synthesized with the linker 1,1'-(trans-2-butene-1,4-diyl)bis-1,2,4-triazole (tbbt) and structurally investigated. The structure of complexes 1-4 is composed of three interpenetrating, symmetry-related 3D networks. Each individual 3D network forms a primitive, nearly cubic lattice (pcu) with BF4- or ClO4- anions present in the interstitial spaces. The structure of compounds 5 and 6 is composed of two-dimensional sql layers, which are parallel to each other in the AB stacking type. These layers are interpenetrated by one-dimensional chains, both having the same formula unit, [M(NCS)2(tbbt)2] (M = Fe, Co). The structure of compound 7 consists of parallel, two-dimensional sql layers in the ABCD stacking type. The interpenetration in 1-6 is not controlled by π-π-interactions between the triazole rings or C=C bonds, as could have been expected, but by (triazole)C-H⋯F4B, C-H⋯O4Cl, and C-H⋯SCN anion hydrogen bonds, which suggests a template effect of the respective non-coordinated or coordinated anion for the interpenetration. In 7, the (triazole)C-H⋯Br anion interactions are supplemented by O-H⋯O and O-H⋯Br hydrogen bonds involving the aqua ligand and crystal water molecules. It is evident that the coordinated and non-coordinated anions play an essential role in the formation of the networks and guide the interpenetration. All iron(II) coordination networks are colorless, off-white to yellow-orange, and have the metal ions in the high-spin state down to 77 K. Compound 5 stays in the high spin state even at temperatures down to 10 K.

Tautomeric equilibrium and spectroscopic properties of 8-azaguanine revealed by quantum chemistry methods.

8-azaguanine is a triazolopyrimidine nucleobase analog possessing potent antibacterial and antitumor activities, and it has been implicated as a lead molecule in cancer and malaria therapy. Its intrinsic fluorescence properties can be utilized for monitoring its interactions with biological polymers like proteins or nucleic acids. In order to better understand these interactions, it is important to know the tautomeric equilibrium of this compound. In this work, the tautomeric equilibrium of all natural neutral and anionic compound forms (except highly improbable imino-enol tautomers) as well as their methyl derivatives and ribosides was revealed by quantum chemistry methods. It was shown that, as expected, tautomers protonated at positions 1 and 9 dominate neutral forms both in gas phase and in aqueous solution. 8-azaguanines methylated at any position of the triazole ring are protonated at position 1. The computed vertical absorption and emission energies are in very good agreement with the experimental data. They confirm the validity of the assumption that replacing the proton with the methyl group does not significantly change the positions of absorption and fluorescence peaks.

Computational Manifestation of Nitro-Substituted Tris(triazole): Understanding the Impact of Isomerism on Performance-Stability Parameters.

Density functional theory (DFT) methods were used to design a series of energetic dinitro-tris(triazole) isomers by altering the triazole rings and -NO2 groups. The impact of three nitrogen atoms' position in the tris(triazole) scaffold on energy content, performance, and stability was discussed. Based on computed heats of formation and densities, the detonation properties were predicted using the thermochemical EXPLO5 (v6.06) code. Using the bond dissociation energy of the longest C-NO2 bond, the thermal stability was investigated. The mechanical sensitivities were estimated and correlated with RDX and HMX using maximum heats of detonation (Q), free void (ΔV) in the lattice of the crystalline compound, and total -NO2 group charge. Among the designed series, compounds O4, R1, R3, and R4 display high heats of formation (>450 kJ/mol), high densities (>1.92 g/cm3), good detonation performances (D > 8.76 km/s and P > 32.0 GPa), and low sensitivities. Our findings suggest that the isomeric tricyclic triazole backbone could be a promising platform for developing new high-performing and thermostable energy materials.

Benzimidazole-Triazole Hybrids as Antimicrobial and Antiviral Agents: A Systematic Review.

Bacterial infections have attracted the attention of researchers in recent decades, especially due to the special problems they have faced, such as their increasing diversity and resistance to antibiotic treatment. The emergence and development of the SARS-CoV-2 infection stimulated even more research to find new structures with antimicrobial and antiviral properties. Among the heterocyclic compounds with remarkable therapeutic properties, benzimidazoles, and triazoles stand out, possessing antimicrobial, antiviral, antitumor, anti-Alzheimer, anti-inflammatory, analgesic, antidiabetic, or anti-ulcer activities. In addition, the literature of the last decade reports benzimidazole-triazole hybrids with improved biological properties compared to the properties of simple mono-heterocyclic compounds. This review aims to provide an update on the synthesis methods of these hybrids, along with their antimicrobial and antiviral activities, as well as the structure-activity relationship reported in the literature. It was found that the presence of certain groups grafted onto the benzimidazole and/or triazole nuclei (-F, -Cl, -Br, -CF3, -NO2, -CN, -CHO, -OH, OCH3, COOCH3), as well as the presence of some heterocycles (pyridine, pyrimidine, thiazole, indole, isoxazole, thiadiazole, coumarin) increases the antimicrobial activity of benzimidazole-triazole hybrids. Also, the presence of the oxygen or sulfur atom in the bridge connecting the benzimidazole and triazole rings generally increases the antimicrobial activity of the hybrids. The literature mentions only benzimidazole-1,2,3-triazole hybrids with antiviral properties. Both for antimicrobial and antiviral hybrids, the presence of an additional triazole ring increases their biological activity, which is in agreement with the three-dimensional binding mode of compounds. This review summarizes the advances of benzimidazole triazole derivatives as potential antimicrobial and antiviral agents covering articles published from 2000 to 2023.

Thermal and oxidative syntheses, structure, and optical properties of 2,6,8-trisubstituted 1,2,3-triazolo[4′,5′:3,4]pyrazolo[1,5-a]pyrimidin-2-ium-1(3)-ides

This study reports the unexpected synthesis of eight examples of a new heterocyclic system, which is composed of a charged triazole ring fused to the pyrazolo[1,5-a]pyrimidine, named 2,8-(diaryl)-6-(trifluoromethyl)-[1,2,3]triazolo[4′,5′:3,4]pyrazolo[1,5-a]pyrimidin-2-ium-1(3)-ides (2). Compounds 2 were successfully synthesized from the reactions of E-3-(aryldiazenyl)-7-(trifluoromethyl)-pyrazolo[1,5-a]pyrimidin-2-amines (1) in yields of up to 85% by employing two different method: thermal azide decomposition and oxidative cyclization. In general, derivatives 2a–h presented absorption bands at the ultraviolet region (250–380 nm) and green emission properties with large Stokes shifts. Moreover, TD-DFT calculations were performed, and redox analysis was conducted by cyclic voltammetry.

Synthesis of Bisubstrate Analogues for RNA Methylation Studies using two Transition-Metal-Catalyzed Reactions.

RNA methyltransferases (RNA MTases) are a family of enzymes that catalyze the methylation of RNA using the cofactor S-adenosyl-L-methionine. While RNA MTases are promising drug targets, new molecules are needed to fully understand their roles in disease and to develop effective drugs that can modulate their activity. Since RNA MTases are suitable for bisubstrate binding, we report an original strategy for the synthesis of a new family of m6A MTases bisubstrate analogues. Six compounds containing a S-adenosyl-L-methionine (SAM) analogue unit covalently tethered by a triazole ring to the N-6 position of an adenosine were synthesized. A procedure using two transition-metal-catalyzed reactions was used to introduce the α-amino acid motif mimicking the methionine chain of the cofactor SAM. First, a copper(I)-catalyzed alkyne-azide iodo-cycloaddition (iCuAAC) reaction afforded the 5-iodo-1,4-disubstituted-1,2,3-triazole which was functionalized by palladium-catalyzed cross-coupling to connect the α-amino acid substituent. Docking studies of our molecules in the active site of the m6A ribosomal MTase RlmJ show that the use of triazole as a linker provides additional interactions and the presence of the α-amino acid chain stabilizes the bisubstrate. The synthetic method developed here enhances the structural diversity of bisubstrate analogues to explore the active site of RNA modification enzymes and to develop new inhibitors.

A novel [1,2,4]triazolo[1,5-a]pteridine framework: Synthesis, photophysical properties and material studies

The synthesis of novel [1,2,4]triazolo[1,5-a]pteridine (TPt) derivatives was carried out starting from [1,2,4]triazolo[1,5-a]pyrimidine-6,7-diamines and 1,2-dicarbonyl compounds. For obtained TPt DFT/TD-DFT calculations were performed with subsequent complex photophysical and electrochemical studies. The substituent in the pyrazine ring of TPt framework proved to have a higher effect on photophysical properties than that in the triazole ring. The fluorescence quantum yields of studied compounds were generally low (3–23%). However, it was shown that some of TPt was sensitive to trace amounts of organic peroxides (about 100 ppm), which will make it possible to create test systems based on them. On the other hand, low-lying HOMO energy levels and the energy gap values of TPt (2.63 eV < E0-0 < 2.97 eV) as well as the electron mobility in solid-state films measured by the conventional CELIV technique (approximately 10−4 cm2 V−1 s−1) make these materials promising for the further use in organic electronic devices.

Synthesis and X-ray Crystal Structure Analysis of Substituted 1,2,4-Triazolo [4’,3’:2,3]pyridazino[4,5-b]indole and Its Precursor

The hit compound 1,2,4-triazolo[4’,3’:2,3]pyridazino[4,5-b]indole 3 was synthesized from the reflux of 4-amino-5-indolyl-1,2,4-triazole-3-thione 1 with 4′-bromoacetophenone 2 in methanol catalyzed by concentrated HCl and the desired final molecule was obtained by recrystallization from methanol. The suggested structures of compounds 1 and 3 based on the spectral characterizations were confirmed by X-ray single crystal diffraction analysis. Compound 3 crystallized in the triclinic crystal system and P-1 space group with a = 5.9308(2) Å, b = 10.9695(3) Å, c = 14.7966(4) Å, α = 100.5010(10)°, β = 98.6180(10)°, and γ = 103.8180(10)°. On the other hand, the crystal system of 1 is monoclinic, where a = 6.23510(10) Å, b = 26.0156(4) Å, c = 12.4864(2) Å, β = 93.243(2)° and the space group is P21. The triazole and indole rings are found twisted from each other in both compounds. The twist angle is higher in 3 (12.65°) than 1 (4.94–7.22°). In the case of the former, the H…H (39.6%), H…C (22.0%), N…H (12.8%) and Br…H (13.2%) contacts are the most dominant while the C…C, C…H, Br…H, N…H and S…S contacts have the characteristics of strong interactions. In the latter, the C…H, N…H, S…H, S…S, and C…C contacts are the most important. In this case, the percentages of the H…H, C…H, N…H and S…H contacts are in the range of 34.9–37.4, 20.5–24.0, 12.2–13.6, 14.0–15.8, respectively. In both systems, the shape index and curvedness of surfaces confirmed the presence of π–π stacking interactions.

Synthesis, antibacterial screening and computational studies of quinazoline-4 (3H)-one-triazole conjugates

A novel series of quinazoline-4 (3H)-one-tagged triazole conjugates were synthesised using the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) methodology. All synthesized compounds were structurally elucidated with the help of 2D-NMR (HMBC, HSQC, COSY) techniques and other spectral evidence. The in vitro antibacterial activities of these compounds were evaluated and compared with commercial drugs ciprofloxacin, ampicillin, and levofloxacin. Four compounds (4a, 4d, 4g, and 4i) of the series exhibited potent activity and selectivity against the gram-negative bacterial strains. Amongst these, 4i emerged as the most active conjugate with almost 12-fold superior activity to ampicillin against Klebsiella pneumoniae (gram-negative), one of the most challenging multidrug-resistant strains worldwide. Structure-activity relationship (SAR) analysis further revealed that the incorporation of a triazole ring incredibly increased the antibacterial activity of quinazoline Schiff bases towards the gram-negative bacteria. Moreover, the para-positioning of strong electron-donating (–OCH3) and electron-withdrawing (-NO2) groups at the phenyl ring of the triazole ring positively influenced the antibacterial activity, whereas the meta-substitution generally decreased the antibacterial activity of the conjugates. Furthermore, molecular docking studies were conducted to explore the binding characteristics of these compounds in the binding site of DNA gyrase (Staphylocouccus aureus).

Synthesis, α-Glucosidase inhibitory activity and docking studies of Novel Ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives

In this work, a novel series of pyridazine-triazole hybrid molecules were prepared and evaluated as inhibitors of rat intestinal α-glucosidase enzyme. Amongst all newly synthesized compounds, 10k showed good inhibition in the series with IC50 value of 1.7 µM which is 100 folds stronger than positive control, acarbose. The cytotoxicity revealed that this compound is not toxic against normal cell line, HDF. The docking studies showed that triazole ring plays an important role in the binding interactions with the active site. The insertion of compound 10k into the active pocket of α-glucosidase and formation of hydrogen bonds with Leu677 was observed from docking studies. The kinetic studies revealed that this compound has uncompetitive mode of inhibition against α-glucosidase enzyme.

Excited state dynamics of 1,2,4-triazolyl-thio-pentane-2,4-dione system and their conversion to biologically active novel triazole-S-pyrazole hybrids

The current study focuses on designing and synthesis of novel 1,2,4-triazole appended pyrazoles linked to each other through sulphur atom. Herein we report the condensation of nicotinic hydrazide and isonicotinic hydrazide with aryl isothiocyanate derivatives to obtain carbothioamides which are cyclised to yield 4-aryl-5-(pyridinyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione derivatives under alkaline conditions. Further, condensation of thiones with 3-chloro-pentane-2,4-dione generated novel 1,2,4-triazolyl-thio-pentane-2,4-dione system which was studied for keto-enol tautomerism with the help of spectral data (FT-IR, NMR and Mass). Low energy barrier between three different tautomers (chelated enol, keto, non-chelated enol) resulted in transformation of chelated enol ⇌ non-chelated enol ⇌ keto form upon UV-irradiation. Solvent effects on excited state intramolecular proton transfer (ESIPT) in dione 5a have been studied and the experimental findings were documented with TD-DFT studies. The generated 1,3-diketones were treated with hydrazine hydrate to obtain triazolyl-S-pyrazole hybrids 6. Structure of the synthesized compounds was identified on the basis of spectroscopic data. Single crystal X-ray diffraction (SC-XRD) studies of the representative compound 6a predicts the strong intermolecular hydrogen bonding interaction between N2H2 of pyrazole ring of one molecule and N4 of triazole ring (N2H2…N4) of the other molecule which accounts for the crystal stability. Moreover, triazolyl-S-pyrazole hybrids were also assessed for their antibacterial activities and some derivatives have shown promising activity against E. coli.

Multivariate design and application of novel molecularly imprinted polymers selective for triazole fungicides in juice and water samples

In the present study, novel molecularly imprinted polymers were prepared using penconazole as template and different combinations of functional monomers (acrylic acid (AA) and N-isopropylacrylamide (NIPAM)) and cross-linkers (ethylene glycol dimethacrylate (EGDMA) and trimethylolpropane trimethacrylate (TRIM)), according to a Plackett-Burman design of experiments. Materials were fully characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and nitrogen adsorption analysis. Rebinding behaviors in solution were studied both at the equilibrium (Langmuir, Freundlich and Temkin models), and at the non-equilibrium (pseudo-first, pseudo-second order kinetics). Materials were further tested as sorbents for dispersive solid phase extraction (d-SPE) on apple juice for multicomponent recovery of triazole fungicides at trace level, testing several variations of extraction parameters (juice pH, amount of sorbent, adsorption time, desorption solvent, desorption time) leading to the selection of the best materials and simultaneously of the best extraction conditions. MIPs synthesized with NIPAM showed significatively higher affinity for triazole pesticides in apple juice than the ones synthesized with AA, while no differences emerged for the two cross-linkers employed (EGDMA, TRIM). Selectivity was also assessed, testing MIPs as d-SPE sorbents in undiluted apple juice spiked with triazole pesticides concurrently with other interfering compounds. The newly developed NIPAM-based penconazole-imprinted MIPs showed an excellent recognition mechanism towards compounds containing the triazole ring, and significatively lower recoveries for other compounds. The developed analytical procedure based on molecularly imprinted polymer dispersive solid phase extraction and liquid chromatography coupled with mass spectrometry (MIP-d-SPE-LC-MS) was validated for selective enrichment and determination of triazole compounds in apple juice samples and river water samples with good recoveries (94.67%–109.03% for river water, 89.79%–110.23%, for apple juice), high repeatability (RSD% < 3.97 for river water, RSD% < 4.85 for apple juice), and reproducibility (RSD% < 5.95 for river water and RSD% < 7.14 for apple juice).

COMPLEX FORMATION OF SILVER(I) WITH 1,2,3-BENZOTRIAZOLE. PROTONIZATION CONSTANTS OF 1,2,3-BENZOTRIAZOLE

The acid–base properties of 1,2,3-benzotriazole (Bta) at 25 °C and I = 0.1 mol/l KCl were studied by the pH-metric method in an aqueous solution. It has been established that in the strongly acidic region of the solution, one of the two nitrogen atoms of the pyridine type of the Bta triazole rings undergoes protonation, and at high pH values, hydrogen abstraction occurs from the NH fragment of the molecule. The obtained values of the protonization constants of 1,2,3-benzotriazole are: log K1 = 8.27 and log K2 = 0.65. Using the potential of a silver electrode, the equilibria of silver(I) complexation with 1,2,3-benzotriazole were studied. The data obtained indicate that Ag+replaces the hydrogen ions of the ligand molecule and forms complexes of the following composition AgBta and AgBta2– with stability constants equal to log β1 = 8.50 (AgBta) and logβ2 = 12.65 (AgBta2–), respectively.

Design, Synthesis, and Biological Evaluation of 1,2,4-Triazole Derivatives as Potential Antimicrobial Agents

In this study, we aimed to develop new biologically active compounds with antibacterial properties. 4-amino-5-methyl-2H-1,2,4-triazol-3(4H)-one (1) was converted to the corresponding Schiff bases (2) with the reaction with a 4-anis aldehyde. Acetic acid ethyl esters containing [1,2,4] triazole ring (3) were synthesized by the condensation of compounds (2) with ethyl bromoacetate in basic media. The reaction of compounds (3) with hydrazine hydrate led to the formation of acid hydrazides (4). The reaction of hydrazide (4) with phenyl isothio - and phenyl isocyanate produced the corresponding carbothioamide (5a) and carboxamide (5b). The basic treatment of carbothioamide (5a) and. carboxamide (5b) produced 1,2,4-triazole (6a, 6b) compounds, respectively. The reactions of ( (6b) with norfloxacin and ciprofloxacin in the presence of formaldehyde afforded the corresponding Mannich bases( 7a, 7b). The structural assignments of the new compounds were based on elemental analysis and spectral (IR, 1H-NMR, and 13C-NMR) data. All newly synthesized compounds were screened for their antimicrobial activity. The in vitro antimicrobial activities of the compounds were evaluated against pathogenic microorganisms, and compounds 7a and 7b were found the most effective antimicrobial activity.

Photochemical behavior and photo-induced toxicity of chiral pesticides and their chiral monomers in aqueous environment

The photochemical behaviors of chiral pollutants in aqueous solutions are rarely studied using chiral monomers, which may hamper their precise risk assessment and lead to suspicious conclusions. In this study, we systematically investigated the phototransformation behavior and toxicity evolution of two widely used chiral pesticides (triadimefon (TF) and triadimenol (TN)) at enantiomer and diastereomer levels, and proposed a calculation method of total photolysis rate constants of chiral mixture. Results show that TF and TN could be photodegraded faster in pure water than in natural waters, and the observed photolysis rate constants (kobs) of TN with two chiral centers exhibit enantioselectivity, i.e., kobs(TN-RS) = kobs(TN-SR) > kobs(TN-RR) = kobs(TN-SS). The photolysis of TF and TN mainly occurs through their excited singlet and triplet states, respectively. Their photodegradation pathways mainly include dechlorination and elimination of triazole ring. TF could also undergo ether bond cleavage. It is also found that, both TF and TN exhibit photo-induced toxicity to V. fischeri, due to the generation of more toxic products than parent compounds. Furthermore, TN exhibits enantioselective photo-induced toxicity after 240-min irradiation, which could be ascribed to the formation of chiral products. These results could benefit the understanding of enantioselective environmental behavior of chiral pollutants.

Synthesis, cytotoxicity and QSAR studies of indolic cannabinoid-triazole hybrids

Twenty-two novel hybrid compounds of indolic cannabinoids and 1,2,3-triazoles were obtained in yields greater than 69%. To this aim, we employed a 1,3-dipolar cycloaddition between terminal alkynes attached to a cannabinoid core and organic azides. These compounds evaluated in vitro for their antiproliferative activity against MCF7 and MDA-MB-231 mammary tumor cells. Also, cytotoxicity towards the normal cell line MCF10A was assessed to estimate selectivity. Twelve compounds showed cytotoxic activity IC50<100 μM. Derivative 18j, which bears an alkyl chain at N-1 triazole ring, was found to be the most active compound, displaying IC50 of 2.8 μM and 4.4 μM against MCF7 and MDA-MB-231 cell lines, respectively, and displaying 3.0-fold less cytotoxic towards normal cell line MCF10A. The best result combining activity and selectivity was found for derivative 18a (benzyl triazole substituted), which showed high cytotoxicity against tumor cell lines (MCF7-IC50 = 8.3 ± 0.4 μM; MDA-MB-231-IC50 = 7.1 ± 0.1 μM) and was not active against the tested normal cell line. QSAR models and molecular docking using Mitogen-activated protein kinase (MAPK) revealed that the triazole ring plays an important role in the antiproliferative activity displayed by the novel compounds, suggesting molecular hybridization as a successful approach. In addition to their high cytotoxicity, the most active derivatives 18a and 18j might also present drug like properties according to predicted ADME parameters, becoming promising compounds for further development of anticancer agents.