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The article provides a comprehensive overview of various synthetic approaches to 1,2,3-triazoles, focusing on up-to-date procedures from 2000 to 2023. The significance of 1,2,3-triazoles in pharmaceuticals and their diverse applications in different fields is highlighted. The text covers classical methods as well as modern approaches, including Cu-catalyzed cycloaddition reactions and metal-free methods, under microwave, ultrasound, and continuous flow conditions. The review emphasizes the importance of click chemistry in simplifying and enhancing the synthesis of 1,2,3-triazoles for future molecular diversity explorations. [Extracted from the article]

In search of new active molecules, a small focused library of novel 1,2,3-triazoles based chalcone derivatives has been efficiently prepared via the click chemistry approach. All the synthesized compounds were characterized with the help of IR, 1H NMR, 13C NMR and mass spectroscopic techniques. The synthesized novel 1,2,3-triazoles based chalcone derivatives evaluated for their anti-inflammatory and antioxidant activity. Furthermore, molecular modeling study could support these outcomes by demonstrating very good binding affinities at the active site of the cyclooxygenase 2 (COX-2) iterating the potential of this scaffold for further optimization. [ABSTRACT FROM AUTHOR]

We have synthesized and characterized N-substituted-1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carbohydrazide derivatives and were evaluated for their antibacterial activity against Staphylococcus Aureus, Micrococcus Luteus, Bacillus subtilis and Gram-negative Escherichia Coli, Pseudomonas aeruginosa and Flavobacterium Devorans pathogens and found that any modification is done at C-3 position then the activity of quinolone scaffold is decreased. This shows that presence of carboxylic acid group at C-3 position is very important for antibacterial activities. To gain more molecular insight into the binding interaction of the synthesized compounds, docking studies with to S. aureus DNA gyrase (PDB: 2XCT) were conducted. Based on its potential anti-bacterial properties, the most active molecule, 5a, was submitted to molecular docking simulations using Schrödinger Glide software. The fluoroquinolones mechanism of action is entirely compatible with the binding interaction of the compound 5a. Further, all the synthesized compounds tested for In Silico ADME prediction and observed that all the compounds followed the criteria for orally active drug and therefore, these compounds can be further developed an oral drug candidate. [ABSTRACT FROM AUTHOR]

In search of new biologically potent molecules a small focused library of new guanidine-1,2,3-triazole hybrid derivatives were synthesized via Organocatalytic enolate- mediated azide-carbonyl [3 + 2] cycloaddition yielding a highly functionalized triazole core structure. The synthesis of all the derivatives were confirmed by spectral analysis 1H NMR, 13C NMR and MS. The new guanidine-1,2,3-triazole conjugates were found to exhibit promising anti-inflammatory and antioxidant activity. The anti-inflammatory activity screened by membrane stabilization method summarizes the four potential conjugates 5c, 5f, 5h and 5g to be potent in comparison with standard drug Diclofenac sodium (DFS). The conjugates were also assessed for antioxidant potential by DPPH method. Among all the synthesized compounds, the compounds 5d, 5f, 5g and 5h exhibited potent antioxidant activity. Molecular docking study was performed to gain insight into the putative binding mode and binding strength of these compounds with the target enzyme Cyclo-oxygenase (COX-2) enzyme. The in vitro and in silico studies together with simpler designing and synthesis strategy via Organocatalytic enolate- mediated azide-carbonyl [3 + 2] cycloaddition followed by a two-component reaction with guanidine in basic conditions rationalize guanidine-1,2,3-triazole hybrid derivatives as easily assessable novel therapeutic agents. [ABSTRACT FROM AUTHOR]

In search of new active molecules, a small focused library of 1,2,3-triazoles based 2,4-thiazolidinedione derivatives has been efficiently prepared via the click chemistry approach. Several derivatives were exhibited excellent anti-inflammatory activity compared to the standard drug. Further, the synthesized compounds were found to have potential antioxidant activity. Furthermore, to rationalize the observed biological activity data, the molecular docking study has also been carried out against the active site of inflammation enzyme PPARγ, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of the in vitro and in silico study suggest that the triazole incorporated 2,4-thiazolidinedione derivatives may possess the ideal structural requirements for the further development of novel therapeutic agents. [ABSTRACT FROM AUTHOR]

A novel series of asymmetric of (E)-3-(4-(benzyloxy) phenyl)-2-((substituted benzylidene) amino)-1-(thiazolidin-3-yl) propan-1-one derivatives (AAP-1 to AAP-10) have been efficiently synthesized from (S)-2-amino-3-(4-(benzyloxy)phenyl)-1-(thiazolidin-3-yl)propan-1-one (4) and various substituted aldehydes by conventional as well as microwave irradiation method. The structure of newly synthesized compounds were confirmed by IR, 1H NMR, 13C NMR, and Mass spectroscopic methods, further evaluated for their in vitro antimicrobial activities. Among these series, the compounds AAP-2, AAP-4, AAP-5, AAP-7, AAP-8 AAP-9, and AAP-10, showed excellent antibacterial activities against Gram-positive bacteria like Staphylococcus aureus (SA), Lysinibacillus sphaericus (LS), Bacillus subtilis (BS) and Klebsiella aerogenes (KA), Pseudomonas Aeruginosa (PA), Chromobacterium violaceum (CV) as Gram-negative bacteria as compared to standard Ciprofloxacin. The compounds AAP-1, AAP-4, AAP-5, AAP-6, AAP-7, and AAP-8 exhibited good antifungal activities against Fusarium oxysporum (FO), Rhizoctonia solani (RS), Colletotrichum capsici (CC) strains as compared to standard Fluconazole. Molecular docking studies of final compounds were performed using Auto Dock Vina software against Lanosterol 14α-demethylase (CYP51A1) enzyme and crystal 4WMZ and showed effective binding affinity of these molecules with enzymes. Quantitative structure toxicity relationship study of target compounds were studied by various computational animal models and defined oral rat LD50 values for cytotoxicity. The AAP-2, AAP-4, AAP-5, and AAP-7 to AAP-10 showed low toxicity. In addition, the pharmacokinetic of target compounds were studied and revealed acceptable good drug-likeness score properties as well as follow Lipinski's rule of five. [ABSTRACT FROM AUTHOR]

An efficient method developed for the synthesis of asymmetric (S)-N-benzylidene-2-(benzyloxy)-1-(5-(pyridin-2-yl)-1,3,4-thiadiazol-2-yl)ethanamine derivatives with excellent yield in short reaction time. The antioxidant and antimitotic activities were estimated and strongly correlated with the potential of Ascorbic acid and Methotrexate respectively. All the synthesized molecules were characterized using various spectral techniques including FTIR, 1H NMR, 13C NMR, and Mass spectrometry. The drug-likeness properties were studied using in silico ADME parameters. All the compounds have an acceptable range of values which indicated good drug-like characteristics based on Lipinski's rule of five and to be orally active. The present method is quite easy along with simple operation and offers many benefits including short reaction time, easy work-up, excellent yield, reduced waste production as well as cost effective. In addition structure-activity relationships of AP-1 to AP-10 derivatives have been described. [ABSTRACT FROM AUTHOR]

A series of new benzimidazole incorporated 3,5-bis (arylidene)-4-piperidones were synthesized by using aryl aldehydes, piperidinone, 2-(chloromethyl)-benzimidazole and DBU acetate [DBUH][OAc] act as a catalyst under solvent free condition in excellent yields. The synthesized compounds were screened for their in vitro antimycobacterial activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. The compounds 4a, 4b, 4e, 4i, 4k and 4l are highly potent against both the strains. Most of the active compounds are non-cytotoxic against MCF-7, A549, HCT 116 and THP-1 cell lines. Furthermore, a molecular docking study of these compounds was carried out to investigate their binding pattern with the target, active site of mycobacterial enoyl-acyl carrier protein reductase (Inh A). Therefore, these compounds can be subjected for further optimization and drug development which could give promising chemical leads for treatment of TB. [ABSTRACT FROM AUTHOR]

We have developed a convenient one-pot multicomponent synthesis of highly functionalized [1,6]-naphthyridines under solvent free condition using [Et3NH][HSO4] in excellent yield. This protocol offers several advantages, including short reaction time, simple experimental workup procedure and no toxic byproducts, avoids the use of toxic organic solvents and anhydrous conditions. Further. we have screened the synthesized naphthyridines for in vitro antibacterial, antifungal and antioxidant activity. Furthermore, a molecular docking study of these compounds was carried out to investigate their binding pattern with the target, β-Ketoacyl-acyl carrier protein synthase III (FabH). Finally, the ADME parameters for these compounds showed good drug like properties and can be developed as oral drug candidates. [ABSTRACT FROM AUTHOR]

A new series of 2-(4,5,6,7-tetrahydrobenzo[c]isoxazol-3-yl)-4H-chromen-4-ones 5a-e were synthesized from 1-(2-hydroxyphenyl)-3-(4,5,6,7-tetrahydrobenzo[c]isoxazol-3-yl)propane-1,3-diones 4a-e in presence of acetic acid and conc. HCl. Compounds 4a-e were synthesized by Baker-Venkataraman rearrangement from 2-acetylphenyl 4,5,6,7-tetrahydrobenzo[c]isoxazole-3-carboxylate 3a-e in presence of pyridine and KOH and compounds 3a-e were synthesized from 4,5,6,7-tetrahydrobenzo[c]isoxazole-3-carboxylic acid 1 and substituted 2-hydroxy acetophenone 2a-e. All the synthesized compounds were characterized with the help of IR, 1H NMR, 13C NMR and mass spectroscopic techniques. All the compounds were screened for their in vitro anti-inflammatory activities. Furthermore, molecular docking study against COX-2 enzyme could provide valuable insight into the binding affinity of these molecules and the type of thermodynamic interactions governing their binding. [ABSTRACT FROM AUTHOR]

An approach toward the synthesis of novel conjugates of 3,5-bis (arylidene)-4-piperidones (DAP) pharmacophore with amide-linkage has been developed via one-pot multicomponent reaction of aryl aldehydes, piperidinone and 2-chloro-N-phenylacetamide using [Et3NH][HSO4] as a catalyst/medium. Both substitutions on arylidene rings and piperidinone nitrogen (substituted 2-chloro-N-phenylacetamide) were varied. The synthesized conjugates were evaluated for their in vitro antitubercular activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. Among the series, compounds 4f, 4g, 4i and 4j showed remarkable broad spectrum antitubercular activity with low IC50 values. Furthermore, computer docking simulations, for the most active conjugates were performed with the active site of mycobacterial enoyl-acyl carrier protein reductase (InhA) support the antitubercular activity. Lower cytotoxicity, high potency and promising activity against MTB and M. Bovis BCG suggest that amide linked DAP could serve as good leads for further modifications and development. [ABSTRACT FROM AUTHOR]

In search for novel compounds targeting Malaria, based on the in silico molecular docking binding affinity data, the novel furans containing pyrazolyl chalcones (3a-d) and pyrazoline derivatives (4a-d) were synthesized. The formation of the synthesized compound were confirmed by spectral analysis like IR, 1H NMR, 13C NMR and mass spectrometry. Compounds with thiophene and pyrazoline ring 4b (0.47 μM), 4c (0.47 μM) and 4d (0.21 μM) exhibited excellent anti-malarial activity against Plasmodium falciparum compared with standard antimalarial drug Quinine (0.83 μM). To check the selectivity furthermore, compounds were tested for antimicrobial activity and none of the synthesized compound exhibited significant potency compared with the standard antibacterial drug Chloramphenicol and antifungal drug Nystatin respectively. So, it can be resolved that the produced compounds show selectively toward antimalarial activity and have the potential to be explored further. [ABSTRACT FROM AUTHOR]

In search of new active molecules, a small focused library of tetrazoloquinoline-based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. Several derivatives were found to be exhibiting promising antimicrobial and antioxidant activity characterized by their lower minimum inhibitory concentration values. All the synthesized compounds exhibited excellent antibacterial activity against Gram negative bacteria E. coli and F. devorans and antifungal activity against C. albicans and A. niger. Further, these compounds were tested for their antitubercular activity against dormant MTB H37Ra and dormant M. bovis BCG using XRMA assay protocol and showed no significant activity. Also, the synthesized compounds were found to have potential antioxidant activity with IC50 range = 12.48–50.20 μg/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against the active site of fungal C. albicans enzyme P450 cytochrome lanosterol 14α-demethylase, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of the in vitro and in silico study suggest that the triazole-incorporated tetrazoloquinolines may possess the ideal structural requirements for further development of novel therapeutic agents. [ABSTRACT FROM AUTHOR]

In search of new active molecules, a small focused library of the synthesis of 3‐(trifluoromethyl)‐1‐(perfluorophenyl)‐1H‐pyrazol‐5(4H)‐one derivatives (4a‐d, 5a‐f, and 6a‐e) has been efficiently prepared via the Knoevenagel condensation approach. All the derivatives were synthesized by conventional and nonconventional methods like ultrasonication and microwave irradiation, respectively. Several derivatives exhibited excellent anti‐inflammatory activity compared to the standard drug. Furthermore, the synthesized compounds were found to have potential antioxidant activity. In addition, to rationalize the observed biological activity data, an in silico absorption, distribution, metabolism, and excretion (ADME) prediction study also been carried out. The results of the in vitro and in silico studies suggest that the 3‐(trifluoromethyl)‐1‐(perfluorophenyl)‐1H‐pyrazol‐5(4H)‐one derivatives (4a‐d, 5a‐f, and 6a‐e) may possess the ideal structural requirements for the further development of novel therapeutic agents. [ABSTRACT FROM AUTHOR]

A series of new 1,2,3-triazolyl chalcones were efficiently synthesized and screened for in vitro antifungal activity against five different fungal strains such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger and Cryptococcus neoformans. All the synthesized chalcones displayed potential antifungal activity against most of the tested fungal strains. Especially, compounds 9b, 9c, 9d and 9g are the most active chalcones and displayed excellent MIC values as compared to standard antifungal drug Miconazole. Based on the structural similarity to known triazole inhibitors of sterol 14α-demethylase (CYP51), molecular docking study was performed to gauze the binding affinity of these chalcones and gains an insight into the plausible mechanism of antifungal action. The synthesized chalcones were also evaluated for in vitro antioxidant activity. All compounds exhibited moderate to excellent antioxidant activity, particularly compounds 9e, 9f, 9g and 9h exhibited excellent antioxidant activity in comparison with standard butylated hydroxytoluene (BHT). Furthermore, the synthesized chalcones were analyzed for ADME properties and showed the potential to build up as good oral drug candidates. [ABSTRACT FROM AUTHOR]