Triazole Analogues Research Articles

Synthesis of CF3CH2‐Amides/Propiolamides/Acrylamides: The TfOH Catalyzed Reactions of Nitrile Compounds with CF3CHN2

AbstractAn efficient and operationally simple protocol to access N‐(2,2,2‐trifluoroethyl)amides/propiolamides and acrylamides via direct conversion of easily accessible nitriles (aryl/alkyl/alkynyl/vinyl) and in situ generated CF3CHN2 as trifluoroethylating reagent has been developed. The protocol offers broad functional group tolerance under mild reaction conditions. Furthermore, the conversion of trifluoroethylated propiolamide into its triazole analog via Ru‐catalyzed [3+2] cycloadditions using BnN3 clearly indicates its versatility in the synthetic applications.

An Integrative Computational Approach for Design and Evaluation of Novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole Analogues as Dual-Action Anti-Retroviral and Anti-Bacterial Agents: Insights into Rational Drug Design Strategies

The development of effective antiretroviral inhibitors (HIV-1 Reverse Transcriptase) and glucosamine-6-phosphate (GlcN6P) agents represent a significant challenge for combating viral infections and related diseases. In this study, we employed a multidisciplinary approach to design and evaluate a series of novel triazole analogs as potential candidates for anti-retroviral and glucosamine-6-phosphate agents. Using molecular docking, we explored the binding interactions between the RSA3 analog and the target proteins implicated in viral replication and glucosamine metabolism. Density functional theory (DFT) employing the 6-311++G(d,p) basis set was utilized for computational analysis, with a subsequent examination of the electronic parameters. The HOMO and LUMO orbitals as well as the molecular electrostatic potential map were investigated using DFT to characterize the reactivity of our molecule. Molecular dynamics simulations were performed to investigate the stability and dynamic behavior of the ligand-protein complex (RSA3) over time (300 ns). Furthermore, we employed MM-GBSA calculations of the compound RSA3 (molecular mechanics generalized band surface area) to estimate the binding free energies (−71.30 ± 7.26 kcal/mol and −67.86 ± 7.09 kcal/mol, respectively) and identified the most promising compounds with high affinity for the target proteins. Additionally, predictive absorption, distribution, metabolism, excretion and toxicity (ADMET) studies of compound RSA3 were conducted to assess its drug-like properties and potential safety profiles of the selected compound. Our results revealed that RSA3 has favorable binding interactions, is a stable complex and has significant binding affinity for target proteins. Moreover, predictive ADMET studies indicated that RSA3 possesses desirable drug-like properties, suggesting its potential for further investigation as an anti-retroviral agent and glucosamine-6-phosphate agent. Overall, this integrative computational approach combining molecular docking, DFT analysis, dynamics simulations, MM-GBSA and predictive ADMET studies provides valuable insights into the design and evaluation of novel triazole analogs with potential therapeutic applications, highlighting the importance of rational drug design strategies in the field of antiretroviral and glucosamine research.

1,4-Diaryl-1,2,3-triazole neolignan-celecoxib hybrids inhibit experimental arthritis induced by zymosan.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes cartilage damage. Anti-inflammatories are widely used in the management of RA, but they can have side effects such as gastrointestinal and/or cardiovascular disorders. Studies published by our group showed that the synthesis of hybrid triazole analogs neolignan-celecoxib containing the substituent groups sulfonamide (L15) or carboxylic acid (L18) exhibited anti-inflammatory activity in an acute model of inflammation, inhibited expression of P-selectin related to platelet activation and did not induce gastric ulcer, minimizing the related side effects. Incontinuation, thepresentstudyevaluated the anti-inflammatory effects of these analogs in an experimental model of arthritisand on the functions of one of the important cells in this process, macrophages. Mechanical hyperalgesia, joint edema, leukocyte recruitment to the joint and damage to cartilage in experimental arthritis and cytotoxicity, spread of disease, phagocytic activity and nitric oxide (NO) and hydrogen peroxide production by macrophages were evaluated. Pre-treatment withL15andL18 reduced mechanical hyperalgesia, joint edema and the influx of leukocytes into the joint cavity after different periods of the stimulus. The histological evaluation of the joint showed that L15andL18reduced cartilage damage and there was no formation of rheumatoidpannus. Furthermore,L15andL18 were non-cytotoxic. The analogs inhibited the spreading, the production of NO and hydrogen peroxide.L15 decreased the phagocytosis. Therefore, L15andL18may be potential therapeutic prototypes to treat chronic inflammatory diseases such as RA.

New LPA1 receptor modulators: Design, synthesis, in-silico, and anticancer studies of triazole and oxadiazole analogs

Lysophosphatidic acid (LPA) is a bioactive signaling molecule that activates LPA1 receptors, which are over expressed in breast cancer. This signaling cascade promotes cancer cell proliferation, survival, metastasis, and angiogenesis. Small molecules that block LPA1 signaling could benefit breast cancer therapy. Novel 1,2,4-triazoles and 1,3,4-oxadiazoles conjugates of benzimidazole/oxazole/thiazole were designed as LPA1 receptor inhibitors, synthesized, and the in-vitro anticancer activity was examined through breast carcinoma cells (MCF-7) by MTT assay. The compounds that reduced the proliferation of MCF-7 cells were further evaluated for their effects on apoptosis, migration, and angiogenesis at IC50 concentration. Suppression of LPA1 protein and gene expression was analyzed by western blot and qRT-PCR techniques. In addition, ligand interactions towards protein and ligand-receptor stability were predicted by molecular interaction studies and molecular trajectory analysis, respectively. The compounds BI-4 and OX-1 exhibited varying levels of cytotoxicity, with IC50 values of 138 μM and 83.25 μM, respectively. They were able to effectively reduce migration and apoptosis as confirmed by AO/EB staining assay. In addition, these compounds were found to significantly reduce the protein and gene expression of LPA1 and angiogenesis genes (Angiogenin-II and Vegf) in MCF-7 cells. Synthesized ligands also showed interactions with the LPA1 receptor and demonstrated good stability in MD simulation. Overall, BI-4 and OX-1 hold promise as potential lead compounds for further exploration of the role of LPA1 receptors in the management of breast carcinoma.

Evaluation of the antifungal action of some new 1,2,4-1h-triazole derivatives against vine anthracnosisin in vitro conditions

The article presents the results of an in vitro study of the toxic effect of some new compounds of the triazole group on the causal agent of grapevine anthracnose – Gloeosporium ampelophagum. The newly synthesized compound (Z)-1-(2,4-dichlorophenyl)-5-methyl-2-(1H-1,2,4-triazol-1-yl)hex-1-en-3-one showed a pronounced antifungal action (99.5 %) compared to the closest triazole analogue – propiconazole.

Computational Exploration of the Structural Requirements of Triazole Derivatives as Colchicine Binding Site Inhibitors

AbstractColchicine inhibits microtubule assembly by preventing tubulin polymerization, making the colchicine binding site a promising target against cancer. The present study focuses on the 3D‐QSAR analysis of 31 triazole analogs. The atom‐based and field‐based QSAR models exhibit significant statistical results for internal and external validations, with the atom‐based 3D‐QSAR model showing a Q2 of 0.658 and R2 of 0.998, and the field‐based 3D‐QSAR model showing a Q2 of 0.658 and R2 of 0.998. The 3D‐QSAR atom‐based pharmacophore model explains biological activity using a six‐point hypothesis (AHHRRR.1), while the field‐based 3D‐QSAR model explains activity based on steric, electrostatic, hydrophobic, and hydrogen bond donor/acceptor fields. Based on the 3D contour maps generated, five new compounds were designed and their ADME/Tox properties predicted. The results suggested that these compounds possess potent pharmacological characteristics. The results of the molecular docking analysis showed that Pred01 and Pred02 had higher docking scores (−6.2417Kcal/mol and −6.5049Kcal/mol, respectively) than compound 15, and they formed notable hydrogen bonds and hydrophobic interactions with active site residues. The MMGBSA results confirmed these findings and emphasized the essential role of van der Waals energy in the binding energy. Moreover, the dynamic stability of the complexes was further supported by MD simulations.

Novel antifungal triazoles with alkynyl-methoxyl side chains: Design, synthesis, and biological activity evaluation

Previous work led to the rational design, synthesis and testing of novel antifungal triazole analogues bearing alkynyl-methoxyl side chains. Tests of in vitro antifungal activity showed Candida albicans SC5314 and Candida glabrata 537 gave MIC values of ≤0.125 μg/mL for most of the compounds. Among these, compounds 16, 18, and 29 displayed broad-spectrum antifungal activity against seven human pathogenic fungal species, two fluconazole-resistant C. albicans isolates and two multi-drug resistant Candida auris isolates. Moreover, 0.5 μg/mL of 16, 18, and 29 was more effective than 2 μg/mL of fluconazole at inhibiting fungal growth of the strains tested. The most active compound (16) completely inhibited the growth of C. albicans SC5314 at 16 μg/mL for 24 h, affected biofilm formation and destroyed the mature biofilm at 64 μg/mL. Several Saccharomyces cerevisiae strains, overexpressing recombinant Cyp51s or drug efflux pumps, indicated 16, 18, and 29 targeted Cyp51 without being significantly affected by a common active site mutation, but were susceptible to target overexpression and efflux by both MFS and ABC transporters. GC-MS analysis demonstrated that 16, 18, and 29 interfered with the C. albicans ergosterol biosynthesis pathway by inhibition at Cyp51. Molecular docking studies elucidated the binding modes of 18 with Cyp51. The compounds showed low cytotoxicity, low hemolytic activity and favorable ADMT properties. Importantly, compound 16 showed potent in vivo antifungal efficacy in the G. mellonella infection model. Taken together, this study presents more effective, broad-spectrum, low toxicity triazole analogues that can contribute to the development of novel antifungal agents and help overcome antifungal resistance.

Discovery of novel phenyl triazole analogs as TRK/ALK dual inhibitors with prospective antitumor effects

The exploration of novel anaplastic lymphoma kinase (ALK) and tropomyosin receptor kinase (TRK) dual inhibitors tended to serve as targeted treatment of cancer. Herein, a series of phenyl triazole derivatives were designed and synthesized as ALK/TRK dual regulators based on structure-based drug design (SBDD) strategy and were evaluated for antiproliferative activity by MTT assay. Accordingly, all compounds showed surprising cytotoxicity with IC50 values below 10 μM on KM12, H2228 and KARPAS299 cell lines. Among them, compound 13a bearing (2-(4-methylpiperazin-1-yl)phenyl)morpholinomethanone moiety was identified as the optimal hit in enzymatic screening with IC50 values of 1.9 nM (TRKA), 7.2 nM (ALK) and 65.2 nM (ALKL1196M), respectively. Furthermore, 13a could inhibit KM12 cell migration and colony formation in a dose dependent manner. Meanwhile, AO/EB staining indicated that the pro-apoptotic effect of 13a was comparable to that of Entrectinib at the dose of 200 nM. Ultimately, the binding model of 13a with TRKA and ALK well established its mode of action which accounted for the superior activities as a promising antitumor candidate.

Synthesis, QSAR study and Pharmacological Evaluation of Novel Triazolidine-2-thione Analogues as Antimicrobial, Anti-inflammatory and Antioxidant agents.

The triazole analogues are molecules of immense attraction because of their wide pharmacological applications. Present research deals with the synthesis of triazole-2-thione analogues and their QSAR study. The synthesized analogs are also evaluated for their antimicrobial, anti-inflammatory, and antioxidant effect. It was revealed that the benzamide analogues (3a, 3d) and triazolidine analogue (4b) were found to be most active against P. aeruginosa and E. coli with pMIC values of 1.69, 1.69 and 1.72, respectively. The antioxidant study of the derivatives showed that 4b was the most active antioxidant with 79% protein denaturation inhibition. The highest anti-inflammatory activity was shown by 3f, 4a and 4f. This study provides certain potent leads for further development of more potential anti-inflammatory, antioxidant and antimicrobial agents.

Triazole‐tethered boswellic acid derivatives against breast cancer: Synthesis, in vitro, and in‐silico studies

A series of new analogues of 3-O-acetyl-11-keto-β-boswellic acid (β-AKBA, 1), 3-O-acetyl-β-boswellic acid (β-ABA, 2) (3–8) and 1H-1,2,3-triazole hybrids of β-AKBA (10a-j) were synthesized by employing highly efficient “Click” chemistry reaction protocol. All synthesized compounds were characterized by 1H-, 13C NMR, and HRMS spectroscopy. The structures of compounds 5 and 6 were unambiguously confirmed by the single crystal X-ray analysis diffraction method. The cytotoxic potential of the synthesized compounds was scrutinized against the triple-negative breast cancer (MDA-MB-231) and normal (MCF-10A) cell lines. Furthermore, all the synthesized derivatives exhibited highly potent anti-proliferative activity with IC50 values ranging from 4.45 to 14.45 µM. Among them, compounds 10j, 10f, and 10i exhibited exceptional inhibitory potency and were found several times more potent than the parent compounds 1 and 2. Additionally, the cheminformatics method was used to identify the potential drug target of the most potent compounds (10j, 10f, and 10i) and their binding mechanism with the selected drug target was predicted through molecular docking. The combined 2D-similarity searching, and structure-based binding investigation predict that these compounds can target CHK1 to produce anti-cancer effects in TNBC. This study lays a good foundation for new triterpenic triazole analogues of boswellic acids and could be effective anticancer leads in breast cancer therapeutics.

Juglans regia Linn.: A Natural Repository of Vital Phytochemical and Pharmacological Compounds

Juglans regia Linn. is a valuable medicinal plant that possesses the therapeutic potential to treat a wide range of diseases in humans. It has been known to have significant nutritional and curative properties since ancient times, and almost all parts of this plant have been utilized to cure numerous fungal and bacterial disorders. The separation and identification of the active ingredients in J. regia as well as the testing of those active compounds for pharmacological properties are currently of great interest. Recently, the naphthoquinones extracted from walnut have been observed to inhibit the enzymes essential for viral protein synthesis in the SARS-CoV-2. Anticancer characteristics have been observed in the synthetic triazole analogue derivatives of juglone, and the unique modifications in the parent derivative of juglone have paved the way for further synthetic research in this area. Though there are some research articles available on the pharmacological importance of J. regia, a comprehensive review article to summarize these findings is still required. The current review, therefore, abridges the most recent scientific findings about antimicrobial, antioxidant, anti-fungal, and anticancer properties of various discovered and separated chemical compounds from different solvents and different parts of J. regia.

Synthesis characterization and evaluation of novel triazole based analogs as a acetylcholinesterase and α-glucosidase inhibitors

A series of novel triazole analogs (10a-k) bearing piperidine were synthesized in an aprotic solvent on the most effective pharmacophore with acetylcholinesterase (AChE) and α-glucosidase inhibitory activity. Triazole analogs (10a-k) were obtained in excellent yields (75–90 %) and characterized by EI-MS, IR, 13C NMR and 1H NMR. The newly synthesized triazole analogs (10a-k) showed potent AChE inhibitory activity in the range of Ki = 0.0155 ± 1.25 µM to 0.557 ± 0.50 µM, IC50 = 0.031 ± 0.85 to 0.537 ± 0.76 µM than Eserine (0.04 ± 0.001 µM) having strong electron-withdrawing fluorine group on the pyridine ring was recorded as a most potent inhibitor of AChE while (%) inhibition against α-glucosidase was ranging between 52.36 ± 1.67 to 85.35 ± 1.39. The kinetic study predicted that triazole analogs (10a-k) followed the un-competitive and mixed type of inhibition against AChE. In silico molecular docking was performed at the active site of the AChE co-crystal structure (PDB ID:1NEN). The results of molecular docking corelate will with the experimental findings.

Carbohydrate-Small Molecule Hybrids as Lead Compounds Targeting IL-6 Signaling.

In the past 25 years, a number of efforts have been made toward the development of small molecule interleukin-6 (IL-6) signaling inhibitors, but none have been approved to date. Monosaccharides are a diverse class of bioactive compounds, but thus far have been unexplored as a scaffold for small molecule IL-6-signaling inhibitor design. Therefore, in this present communication, we combined a structure-based drug design approach with carbohydrate building blocks to design and synthesize novel IL-6-signaling inhibitors targeting glycoprotein 130 (gp130). Of this series of compounds, LS-TG-2P and LS-TF-3P were the top lead compounds, displaying IC50 values of 6.9 and 16 µM against SUM159 cell lines, respectively, while still retaining preferential activity against the IL-6-signaling pathway. The carbohydrate moiety was found to improve activity, as N-unsubstituted triazole analogues of these compounds were found to be less active in vitro compared to the leads themselves. Thus, LS-TG-2P and LS-TF-3P are promising scaffolds for further development and study as IL-6-signaling inhibitors.

Ultrasound-assisted green synthesis of triazole-based azomethine/thiazolidin-4-one hybrid inhibitors for cancer therapy through targeting dysregulation signatures of some Rab proteins

ABSTRACT The overexpression of Rab proteins was linked to cancer development, making this family of proteins an attractive drug target for the identification of novel inhibitors against tumor diseases. In this study, novel triazole-based azomethine/thiazolidin-4-one hybrid analogs were designed, prepared and structurally confirmed by using elemental and spectral techniques, these include FT-IR, MS, and NMR spectra. In addition, in vitro cytotoxic activity was assessed against NCI-60 cancer cell lines. To understand the possible mode of action and drugability, molecular docking studies and drug-likeness were achieved. The docking simulations were performed against various Rab family proteins Rab2a, Rab25, Rab5, and Rab35; promising targets for cancer medication to support the cytotoxicity findings and to further validate the action of new molecules. Furthermore, in silico ADMET screening of the molecules was within the recommended values stated by Lipinski's rule of five (Ro5), indicating their oral bioavailability and therapeutic potentials. Among the newly prepared analogs tested, compounds 4d and 3d exhibited significant antitumor activity against breast, ovarian, lung, and leukemia cancer cell lines. Our findings suggested that azomethine/thiazolidin-4-one moieties incorporated triazole analogs are a promising class of molecular entities for the development of new anticancer therapies, through targeting of some Rab proteins.

Triazoles with inhibitory action on P2X7R impaired the acute inflammatory response in vivo and modulated the hemostatic balance in vitro and ex vivo.

The present study aimed to investigate five triazole compounds as P2X7R inhibitors and evaluate their ability to reduce acute inflammation in vivo. The synthetic compounds were labeled 5e, 8h, 9i, 11, and 12. We administered 500ng/kg triazole analogs in vivo, (1-10µM) in vitro, and 1000mg/kg for toxicological assays. For this, we used in vitro experiments, such as platelet aggregation, in vivo experiments of paw edema and peritonitis in mice, and in silico experiments. The tested substances 5e, 8h, 9i, 11, and 12 produced a significant reduction in paw edema. Molecules 5e, 8h, 9i, 11, and 12 inhibited carrageenan-induced peritonitis. Substances 5e, 8h, 9i, 11, and 12 showed an anticoagulant effect, and 5e at a concentration of 10µM acted as a procoagulant. All derivatives, except for 11, had pharmacokinetic, physicochemical, and toxicological properties suitable for substances that are candidates for new drugs. In addition, the ADMET risk assessment shows that derivatives 8h, 11, 5e, and 9i have high pharmacological potential. Finally, docking tests indicated that the derivatives have binding energies comparable to the reference antagonist with a competitive inhibition profile. Together, the results indicate that the molecules tested as antagonist drugs of P2X7R had anti-inflammatory action against the acute inflammatory response.

Discovery of (R)-2-amino-3-triazolpropanoic acid derivatives as NMDA receptor glycine site agonists with GluN2 subunit-specific activity.

N-Methyl-d-aspartate (NMDA) receptors play critical roles in central nervous system function and are involved in variety of brain disorders. We previously developed a series of (R)-3-(5-furanyl)carboxamido-2-aminopropanoic acid glycine site agonists with pronounced variation in activity among NMDA receptor GluN1/2A-D subtypes. Here, a series of (R)-2-amino-3-triazolpropanoic acid analogues with a novel chemical scaffold is designed and their pharmacological properties are evaluated at NMDA receptor subtypes. We found that the triazole can function as a bioisostere for amide to produce glycine site agonists with variation in activity among NMDA receptor subtypes. Compounds 13g and 13i are full and partial agonists, respectively, at GluN1/2C and GluN1/2D with 3- to 7-fold preference in agonist potency for GluN1/2C-D over GluN1/2A-B subtypes. The agonist binding mode of these triazole analogues and the mechanisms by which the triazole ring can serve as a bioisostere for amide were further explored using molecular dynamics simulations. Thus, the novel (R)-2-amino-3-triazolpropanoic acid derivatives reveal insights to agonist binding at the GluN1 subunit of NMDA receptors and provide new opportunities for the design of glycine site agonists.

Design, synthesis, molecular docking and pharmacological evaluation of novel triazine-based triazole derivatives as potential anticonvulsant agents

Triazine-linked triazole compounds (4a-j) were designed, synthesized, and then examined for their anticonvulsant abilities. Compounds 4e, 4f, 4g, 4i, and 4j displayed significant anticonvulsant activity in both maximum electroshock seizure (MES) and pentylenetetrazole (PTZ) induced seizure during the preliminary screening. The phase II anticonvulsant activity statistics revealed that compounds 4e, 4f, 4g, 4i, and 4j demonstrated excellent activity as compared to the conventional drugs methaqualone and valproate, supporting the potential of these triazine-linked triazole analogues as novel anticonvulsant agents. To take use of the findings, computational parameters including docking analysis and drug-likeness prediction were carried out. Molecular modelling studies supported the essential pharmacophoric information that the structure activity relationship offered. The triazine-linked triazole analogues that were investigated might be viewed as helpful models for future research and derivatization.

New quinoline-based triazole hybrid analogs as effective inhibitors of α-amylase and α-glucosidase: Preparation, in vitro evaluation, and molecular docking along with in silico studies.

The 7-quinolinyl-bearing triazole analogs were synthesized (1d–19d) and further assessed in vitro for their inhibitory profile against α-amylase andα-glucosidase. The entire analogs showed a diverse range of activities having IC50 values between 0.80 ± 0.05 µM to 40.20 ± 0.70 µM (α-amylase) and 1.20 ± 0.10 µM to 43.30 ± 0.80 µM (α-glucosidase) under the positive control of acarbose (IC50 = 10.30 ± 0.20 µM) (IC50 = 9.80 ± 0.20 µM) as the standard drug. Among the synthesized scaffolds, seven scaffolds 12d, 10d, 8d, 9d, 11d, 5d, and 14d showed excellent α-amylase and α-glucosidase inhibitory potentials with IC50 values of 4.30 ± 0.10, 2.10 ± 0.10, 1.80 ± 0.10, 1.50 ± 0.10, 0.80 ± 0.05, 5.30 ± 0.20, and 6.40 ± 0.30 µM (against α-amylase) and 3.30 ± 0.10, 2.40 ± 0.10, 1.20 ± 0.10, 1.90 ± 0.10, 8.80 ± 0.20, 7.30 ± 0.40, and 5.50 ± 0.10 µM (against α-glucosidase), respectively, while the remaining 12 scaffolds 19d, 8d, 17d, 16d, 15d, 7d, 4d, 3d, 1d, 2d, 13d and 6 d showed less α-amylase and α-glucosidase inhibitory potentials than standard acarbose but still found to be active. Structure–activity connection studies also showed that scaffolds with electron-withdrawing groups like -Cl, -NO2, and -F linked to the phenyl ring had higher inhibitory potentials for -amylase and -glucosidase than scaffolds with -OCH3, -Br, and -CH3 moieties. In order to better understand their binding sites, the powerful scaffolds 11d and 9d were also subjected to molecular docking studies. The results showed that these powerful analogs provide a number of important interactions with the active sites of both of these targeted enzymes, including conventional hydrogen bonding, pi–pi stacking, pi–sulfur, pi–anion, pi–pi, pi–sigma, T-shaped, and halogen (fluorine). Furthermore, various techniques (spectroscopic), including 1H, 13C-NMR, and HREI-MS mass, were used to explore the correct structure of newly afforded hybrid scaffolds based on quinoline-bearing triazole ring.

Design, synthesis and evaluation of novel phenanthridine triazole analogs as potential antileishmanial agents.

Aim: To synthesize and screen phenanthridine and 1,2,3-triazole derivatives for antileishmanial activity. Methodology: Synthesized analogs were tested for antileishmanial activity against transgenic strain of Leishmania infantum promastigotes and ex vivo infections. Results: Compounds T01, T08 and T11 revealed significant activity with EC50 <30μm and lacked toxicity in mouse spleen and HepG2 cells. T01 with EC50 3.07μm is fourfold more potent than the drug miltefosine (EC50 12.6μM) against L. infantum promastigotes. Insilico studies indicate that the analogs are nontoxic. A molecular docking analysis was also carried out on the T01 and T08 to investigate the binding pattern at the active site of the chosen target trypanothione reductase. Conclusion: The results of this study reveal that phenanthridine triazoles exhibit antileishmanial activity.

A Concise Synthesis of Triazole Analogues of Lavendustin A via Click Chemistry Approach and Preliminary Evaluation of Their Antiparasitic Activity Against Trypanosoma cruzi

AbstractLavendustin A is a natural product isolated from the actinobacteria Streptomyces griseolavendus that presents a potent inhibitory activity on the Epidermal Growth Factor Receptor Protein Tyrosine Kinase (EGFR PTK). In addition, some of its analogues have also shown potent inhibitory activity against the polymerization of tubulin to microtubules, a pivotal process for the cell mitosis. From strategic structural modifications, two useful unprecedented alkynes bearing lavendustin A pharmacophoric subunit were rapidly accessed. Next, a set of novel triazole analogues of lavendustin A were synthesized in good yields employing CuI‐catalyzed azide‐alkyne cycloadditions (CuAAC) under mild conditions. Furthermore, preliminary evaluation of their biological activity against the epimastigote stage of Trypanosoma cruzi points towards promising trypanocidal properties.