Triazole Research Articles

A Pharmacological Update of Triazole Derivative: A Review.

Recently, a large number of novel heterocyclic compounds and their derivatives have been synthesized, and studies on their biological functions have been conducted. Even though the triazole moiety of this scaffold appears to be fairly small, many researchers are interested in it because of its biological profile and variety of potential uses. Triazole derivatives have been synthesized and published by various researchers as their important characteristic against various diseases. Several researchers are interested in this scaffold because of its biological profile and wide variety of potential uses, even if its triazole moiety seems to be somewhat less. The derivative of this heterocyclic ring produced various biological activities such as anti-inflammatory, anticonvulsant, hypoglycemic, antitubercular, anxiolytic, antimicrobial, antitumor, and anticancer. The current review article focuses on pharmacological profile associated with triazoles and mainly focuses on structural modification done for various targets, along with a brief description of targets.

Construction of Iron-Modified Lignin-Based Nanomicrocapsules for Enhancing the Functionality of Natural Product-Based Pesticides.

To address the issue of low pesticide utilization owing to poor dispersibility, low leaf surface adhesion, and poor transport within plants, this study exploits electrostatic interactions between sodium lignosulfonate (SL) and dodecyltrimethylammonium chloride (DTAC) to induce self-assembly, followed by iron ion (Fe3+) chelation and loading with a natural product-based pesticide, rosin-based triazole derivative (RTD), yielding RTD@SL-DTAC-Fe nanomicrocapsules (NMs). It is worth noting that the presence of Fe3+ enhances the dispersibility of the NMs. The water dispersibility and photostability of RTD are significantly improved after encapsulation, and a stimulus response to laccase is achieved. Leaf-washing experiments confirm the enhanced adhesion of RTD@SL-DTAC-Fe NMs to the surface of rice plant leaves compared to that of free RTD. Fluorescently labeled NMs exhibit bidirectional transport within rice plants, and RTD@SL-DTAC-Fe NMs demonstrates better transport performance than RTD. In vitro and in vivo antifungal tests indicate that encapsulation by NMs significantly enhanced pesticide activity. Field trials demonstrate that NMs exhibited prolonged efficacy compared to RTD. Finally, the safety evaluation confirms the environmental friendliness of the NMs. This study provides valuable insight for optimizing and improving the utilization efficiency and biosafety of natural product-based pesticides.

An Electrochemical Route to Novel N‐benzoyl‐1,2,3‐triazoles and Protein Binding Studies of Selected Triazole Derivatives

AbstractAn electrochemical, cost‐efficient and atom‐economic method for the synthesis of novel, structurally unique N‐benzoyl‐1,2,3‐triazole derivatives has been developed via cascade oxidation‐ 1,3‐dipolar cycloaddition reaction of readily available propargyl alcohol and benzoyl azide. The electro‐oxidation of propargyl alcohol and subsequent cycloaddition was performed in an undivided cell using graphite rod and stainless‐steel plate as inexpensive electrode materials. Numerous 4,5‐disubstituted N‐benzoyl‐1,2,3‐triazoles may be synthesized from milli to multi‐gram scale employing this protocol. The biological significance of few selected triazole derivatives were evaluated via protein binding studies.

Iodide Ion-Promoted Highly Regioselective Triazolization of Aldehydes via Desulfonation-Associated Direct Radical Coupling.

A highly efficient iodide ion (I-)-promoted method for direct α-C(sp2)-H triazolization of aldehydes has been developed for the regioselective synthesis of N2-substituted triazole derivatives. The developed method features the corresponding products in good yields (up to 99%) with an excellent functional group tolerance via an intermolecular oxidative radical coupling. Experimental mechanistic investigations indicate that the reaction proceeds via an I--promoted synergistic desulfonylation process, which provides a high regioselectivity. The developed method provides a direct, metal-free, operationally simple, and highly regioselective approach to C(sp2)-H triazolization from easily accessible aldehydes in air.

DESIGN, SYNTHESIS, IN SILICO STUDIES, AND PHARMACOLOGICAL EVALUATION OF 5-ARYL-4-(CHLOROACETYLAMINO)-3-MERCAPTO-1,2,4-TRIAZOLE DERIVATIVES AS ANTICONVULSANT AGENTS

Objective: In this study, we reported the synthesis of a novel series of 5-aryl-4(chloroacetylamino)-3-mercapto-1, 2,4-triazoles. Methods: These compounds were synthesized to screen for anticonvulsant effects in a Maximal Electroshock Seizure (MES) model and a Subcutaneous Pentylenetetrazole (sc‐PTZ) seizure model in rats. Furthermore, molecular docking studies with gamma-aminobutyric acid and in silico ADME prediction were carried out to determine interactions of these compounds with Benzodiazepine (BZD) receptors and their similarity with standard drugs. The rotarod test was used to evaluate neurotoxicity. Results: 08 out of 40 compounds exhibited neurotoxicity at the maximum tested dose. Most of the compounds showed anti‐MES effects without any signs of neurological deficit. All the tested compounds significantly reduced seizures induced by PTZ compared to the control group. Carbamazepine and phenytoin were used as positive controls for anticonvulsant effects. Compounds 3d, 3h (a diphenylamine derivative of 5-aryl-4(chloroacetylamino)-3-mercapto-1,2,4-triazole), and 4a (a piperidinyl derivative of 5-aryl-4(chloroacetylamino)-3-mercapto-1,2,4-triazole) exhibited greater safety than phenytoin and carbamazepine in terms of neurotoxicity. The docking scores for the identified compounds 3d, 3h and 4a was 6.5133; 6.6558 and 5.6524, respectively. Nearly all the compounds (90%) demonstrated decreased locomotor activity. Conclusion: It is gratifying that the compounds with higher hydrophobicity showed better performance in the seizure models. Many triazole derivatives holding a suitable aryl or alkyl group gave a better anticonvulsant activity in their analogs.

Rhodium-Catalyzed Enantioselective Ring-Openings of Oxabicyclic Alkenes with Azole Nucleophiles.

We report enantioselective ring-openings of oxabicyclic alkenes with azole nucleophiles, generating heterocycle-bearing dihydronaphthalene products. Pyrazoles, triazoles, tetrazoles, and benzo-fused derivatives participate in the ring-opening, with the level of regioselectivity depending on the type and substitution pattern of the heterocyclic partner. Electron-withdrawing azole substituents have a beneficial effect, suppressing the unproductive complexation of a nitrogen with the Rh(I)-bis(phosphine) catalyst.

Aniline Derivatives Containing 1-Substituted 1,2,3-Triazole System as Potential Drug Candidates: Pharmacokinetic Profile Prediction, Lipophilicity Analysis Using Experimental and In Silico Studies

Background: The triazole ring is an attractive structural unit in medicinal chemistry, and chemical compounds containing this type of system in their structure exhibit a wide spectrum of biological activity. They are used in the development of new pharmaceuticals. One of the basic parameters considered in the initial phase of designing potential drugs is lipophilicity, which affects the bioavailability and pharmacokinetics of drugs. Methods: The study aimed to assess the lipophilicity of fifteen new triazole derivatives of aniline using reversed phase thin layer chromatography (RP-TLC) and free web servers. Based on in silico methods, the drug similarity and pharmacokinetic profile (ADMET) of synthesized molecules were assessed. Results: A relationship was observed between the structure of the title compound, including the position of substitution in the aniline ring, and the experimental values of lipophilicity parameters (logPTLC). Most of the algorithms used to determine theoretical logP values showed less sensitivity to structural differences of the tested molecules. All obtained derivatives satisfy the drug similarity rules formulated by Lipinski, Ghose and Veber. Moreover, in silico analysis of the ADME profile showed favorable values of parameters related to absorption.

Advancements in Combating Fungal Infections: A Comprehensive Review on the Development of Azole Hybrid Antifungals.

In this review, we have summarized antifungal agents containing potent azole analogues. The provided literature is related to the development and application of azole derivatives and has been accessed from electronic data bases such as Science direct, Google Scholar, and Pubmed using keywords such as "design, synthesis and evaluation", "azole hybrids", "diazole hybrids", "indazole derivatives", "imidazole derivatives", "triazole derivatives", "tetrazole derivatives" and related combinations. From this review, it was identified that azole derivatives with promising antifungal activity play a vital role in drug discovery and development. The literature revealed that azole derivatives can effectively fight several types of microorganisms, such as Candida albicans, Aspergillus niger, and others. The rational design and structure‒activity relationship of these compounds are discussed in this paper, highlighting their potential as effective therapeutic options against various fungal pathogens. Moreover, this work addresses the challenges and future directions in the development of azole hybrids. The results of docking studies of several of the hybrids that the researchers provided are also summarized. The current work attempts to review such innovations, which may lead to the preparation of novel therapeutics. More research is required to confirm their safety and effectiveness in clinical practices.

The Neuroprotection of 1,2,4-Triazole Derivative by Inhibiting Inflammation and Protecting BBB Integrity in Acute Ischemic Stroke.

The oxidative stress and neuroinflammation are important factors in acute ischemic stroke (AIS). Our former study showed the 1,2,4- triazole derivative (SYS18) had obviously neuroprotection by anti- oxidative stress on rat middle cerebral artery occlusion (MCAO) model. In this study, we continue to investigate its neuroprotection by anti-inflammatory effects and protecting BBB integrity in AIS. First, its effect on acute inflammation was evaluated by the mice model of increased peritoneal capillary permeability. Then, the MCAO cerebral edema models were built to evaluate its neuroprotection by reducing the neurological score, cerebral edema, improving the biochemical indicators, and pathological damage of brain tissue. At the same time, its protection on blood-brain barrier (BBB) integrity was proved by decreasing the BBB permeability and inhibiting glycocalyx degradation and regulating the BBB tight junction proteins expression of matrix metalloproteinase- 9 (MMP- 9) and claudin- 5 in brain tissue. Meanwhile, pharmacokinetic experiments showed that the compound had good BBB penetration. It has some advantages in the intensity of efficacy compared with the marketed drug edaravone. Based on these findings, SYS18 has a strong potential to become a neuroprotectant in the future.

Semisynthetic p-Coumaric Acid Derivatives as Lead Dual Inhibitors Against DPP-IV and GSK-3β for Antidiabetic Therapy.

Type 2 diabetes mellitus is a dramatically increasing global public health challenge. The prevalence is projected almost double, from 194 million in 2003 to 333 million in 2025 with type 2 diabetes mellitus representing approximately 90%-95% of cases. Dual inhibitors for antidiabetic targets is still novel and promising strategy for discovery of more effective therapies. Ester and triazole derivatives of p-coumaric acid were obtained from Williamson synthesis and Microwave-assisted click reaction, respectively. Chemical structures were finely characterized through IR, 1H, and 13C NMR and HRMS. They were tested for their dual inhibitory activity against GSK-3β kinase and DPP-IV. The complexes resulting from docking were used for all-atom molecular dynamics simulations, including the enzymes in the apo form, using the GROMACS 2022.3. Two inhibitors 2 and 5 demonstrated promising inhibition at low and submicromolar against both proteins. Molecular Dynamic simulations revealed that the binding pattern of the control inhibitors were reproduced by p-coumaric acid derivatives 2 and 5 with crucial interactions involving the same residues. The p-coumaric skeleton can be considered as a promising core for GSK-3β kinase and DPP-IV dual inhibitors.

Synthesis, Characterization, Insecticidal Activity and Antibacterial Evaluation of Some Heterocyclic Compounds Containing 1,2,3-Triazoles Moiety

A series of 1,2,3-triazole compounds having thymol or paracetamol moieties have been designed via employing ‘click’ chemistry with copper-catalyzed azide-alkyne cycloaddition reactions. Additionally, the insecticidal characterizations of many designed products were perceived with respect to second & fourth of Spodoptera littoralis instar larvae. Numerous insecticides are revealed as novelties. As a result, numerous triazole derivatives were designed chemically to assist as analogues a comprehensive class of insecticides. With LC50 value of 0.321 mg/L for second larvae instar and LC50=0.627 mg/L four instar larvae, components 10 display the highest insecticidal bioactivity. This article deliberates how to find novel compounds that could be employed as insecticidal components in the future. A few biological and biochemical properties of the compounds produced in a laboratory environment were also examined. This work also addresses the process of finding new compounds that could be used as insecticidal products in the future. Ultimately, the antibacterial effectiveness of each developed component contrary to both Gram-positive & Gram-negative bacteria was observed.

Comparative, anti-infective screening and molecular docking studies of 4-amino-1, 2, 4-triazole derivatives

The rise of drug-resistant bacteria is a problem in medicine. This highlights the need to find new molecules that have anti-infective properties. In this study, thiosemicarbazone derivatives were made using a 4-amino-1,2,4-triazole structure. We have evaluated at the anti-infective activity against E. coli, S. aureus, C. albicans, & M. tuberculosis. Among the compounds tested, 4g showed activity at concentrations of 1 μg/ml & 2 μg/ml against E. coli and S. aureus. The molecule 4c had anti-infective activity at a concentration of 6.25 μg/ml against M. tuberculosis. Four compounds had nitro, anthracene, & chlorine (both mono & disubstituted) groups and were effective against all the bacteria we tested. Analysis of molecular binding was also done to see how these compounds bond with E. coli (PDB ID: 1HSK), S. aureus (PDB ID: 1HSK), C. albicans (PDB ID: 5V5Z), and M. tuberculosis (PDB ID: 4P8H).

Recent Developments Towards the Synthesis of Triazole Derivatives: A Review

Recent Developments Towards the Synthesis of Triazole Derivatives: A Review

Synthesis of new triazole derivatives and their potential applications for removal of heavy metals from aqueous solution and antibacterial activities.

In this paper, triazole derivatives were prepared by a three-step mild reaction using carbon disulfide as starting material. In face of microbial threats, we found that compound 3-cyclopropyl-[1,2,4]triazolo [3,4-b][1,3,4]thiadiazole-6-thiol (C2) has good antibacterial activity, inhibition and clearance ability against biofilms, low hemolytic activity and toxicity, good anti-inflammatory activity. At the same time, we found that B and C series compounds have good metal ion scavenging ability, with removal rates of C series ranging from 47% to 67% and B series ranging from 67% to 87%.

Discovery of highly potent triazole derivatives with broad-spectrum antifungal activity based on Iodiconazole

The widespread use of broad-spectrum antibiotics, the growing number of immunocompromised individuals, and the emergence of drug-resistant strains have resulted in the increasing incidence and mortality of invasive fungal infections. Azole drugs are the primary treatment for invasive fungal infections, and Iodiconazole is a potent azole drug with strong antifungal activity, but its stability is poor. In order to improve stability, a series of triazole compounds containing ethynyl group were designed and synthesized. Most of the compounds showed strong inhibitory activity against pathogenic fungi, among which compound 20l showed excellent inhibitory activity against pathogenic fungi and drug-resistant fungi. Importantly, and the stability of 20l (T1/2 = 30.2 min) was obviously improved compared with Iodiconazole (T1/2 = 4.39 min). In addition, the preferred compound 20l can prevent fungal phase transition and the formation of fungal biofilm, and show satisfactory fungicidal activity. In addition, the compound 20l was almost non-toxic to mammalian HUVEC cell and 293T cell. In vivo pharmacokinetic studies showed that 20l had acceptable pharmacokinetic properties. These results strongly demonstrate that compound 20l was worth further investigation as a potential antifungal inhibitor.

Synthesis of New polymers of Triazole Derivatives

Thiatriazole is an important monomer, whereby it have two types of functional groups, amine and thiol. Within the frame of this work the triazole monomer have been prepared from its oxadiazole. Two type of polymers were prepared from this monomer via condensation with terephthaldehyde and succinyl chloride, whereby the binding units of the resulted polymers are differs, azomethine and amide respectively. Infrared spectroscopy and elemental analysis were used to identified the polymers. DTA, TGA and DSC analysis indicate the thermal history of the polymers. It was shown that polymer (1) was more flexibility than polymer (2) due to the lower Tg value due to the presence of azomethene group. The Tg are (138oC) and (190oC) respectively. Also the DTA, TGA indicates that polymer (2) have high thermal stability than polymer 1 due the presence of the amide group.

Phytotoxic and Cytogenetic Assessment of Glycerol Triazole Derivatives in Model Plants and Weeds.

Weed invasion represents a challenge for farmers, who typically manage it with herbicides. However, this approach raises concerns about environmental and human health, as well as increasing resistance in these plants with continued use. Therefore, exploring alternative methods, such as heterocyclic compounds, triazoles, is essential due to their biological and environmental relevance. This study aimed to evaluate the effects of twelve 1,2,3-triazoles on the germination and early development of Lactuca sativa, Bidens pilosa, and Lolium multiflorum, as well as their impact on cell division in the cells of L. sativa. Triazole derivatives 4a, 4b, 4c, 4g, 4h, 4i, 4k, and 4l exhibited phytotoxicity, showing varying levels of inhibition in germination, germination speed index, and root growth. Chlorinated compounds were the most detrimental to lettuce development. B. pilosa was notably affected by compounds 4h, 4i, 4k, and 4l, while L. multiflorum responded most to triazoles 4c and 4l, with effectiveness comparable to that of the herbicide glyphosate. All derivatives, except 4l, exhibited aneugenic mechanisms of action, and 4a, 4b, 4c, 4e, 4f, and 4g showed clastogenic effects. This study demonstrated the potential of triazoles as effective agents against weed growth, with mechanisms that warrant further investigation for agricultural applications.

Complex Protection of Some Steels in Sulfuric Acid Solutions by 1,2,4-Triazole Derivatives.

The corrosion behavior of steels of various grades in sulfuric acid solutions with the addition of nitrogen-containing corrosion inhibitors has been studied. Compounds containing the 1,2,4-triazole moiety effectively protect low-carbon (St3, St20, 08PS), high-strength (70S2KhA), and stainless steels (1Kh18N9T) not only from corrosion but also from the hydrogen penetration into the metals in concentrated sulfuric acid solutions. In some cases, the degree of steel protection from corrosion by these compounds exceeded 99%. The possibility of creating mixed inhibitors for steel protection containing triazole derivatives and KI has been shown. The rate constants for the main steps of cathodic evolution and hydrogen penetration into steel in sulfuric acid solutions have been determined, and the subsurface concentrations of hydrogen in the metals have been calculated. Triazole derivatives were found to act as inhibitors of hydrogen absorption by steel in H2SO4 solution. The degree of protection of steel from hydrogen absorption can reach 97%. It has been shown that triazole derivatives act as complex inhibitors of steel corrosion in sulfuric acid solutions because, along with strong inhibition of metal corrosion, they prevent hydrogen absorption by steel.

Fluorescent-based bile acid triazole-phenothiazine derivatives: Multiphase detection of biogenic amines and application in spoiled foods

Amines are ubiquitous in biological world, yet are toxic and harmful in nature. To preserve the quality and safety of these packaged meals, it’s critical to identify biogenic amines that are emitted from spoiled meat, fish, or dairy products. To this endeavour, herein we report bile acid based triazole derivative with phenothiazine that are capable of sensing various amines by rapid change of fluorescence colour or intensity. The triazole derivatives exhibit a multiphase sensing platform by effectively sensing amine vapours or solutions in both solid and solution phases. Probes in the vapour state exhibit very quick interaction to primary amines (26 s for CTPTZ) and strong sensitivity to putrescine, which is a common example of biogenic amines (BAs). We have employed our unique sensing triazole derivative as a spoilage indication for meat. It detects biogenic amines from spoiled food and produces an optical response. Significant changes in both visual and luminescent were noted within 4–18 h of packaging at room temperature (∼25 °C). The rapid response that biogenic amines provide to these molecular sensors makes them highly promising for applications in the food packaging industry, medical diagnostics, and other sensory devices.

Development of Mycobacterium tuberculosis Enoyl Acyl Reductase (InhA) Inhibitors: A Mini-Review

This review article delves into the critical role of Enoyl acyl carrier protein Reductase (InhA; ENR), a vital enzyme in the NADH-dependent acyl carrier protein reductase family, emphasizing its significance in fatty acid synthesis and, more specifically, the biosynthesis of mycolic acid. The primary objective of this literature review is to elucidate diverse scaffolds and their developmental progression targeting InhA inhibition, thereby disrupting mycolic acid biosynthesis. Various scaffolds, including thiourea, piperazine, thiadiazole, triazole, quinazoline, benzamide, rhodanine, benzoxazole, and pyridine, have been systematically explored for their potential as InhA inhibitors. Noteworthy findings highlight thiadiazole and triazole derivatives, demonstrating promising IC50 values within the nanomolar concentration range. The review offers comprehensive insights into InhA's structure, structure-activity relationships, and a detailed overview of distinct scaffolds as effective inhibitors of InhA.