Acid Hydrazide Derivatives Research Articles

Synthesis and Characterization of Novel Benzothiazinonic N-Acylhydrazone Derivatives

Several recent research studies have demonstrated that N-acylhydrazones are well known as privileged scaffolds frequently used in the discovery of new potential antiparasitic compounds. The investigation of literature revealed that the synthesis of N˗acylhydrazones bearing the 1,4˗benzothiazin˗3-one pharmacophore has not been described. Therefore, it was considered interesting to attempt the synthesis of new N˗acylhydrazone derivatives containing 1,4˗benzothiazine˗3˗one fragment, thus obtaining a series of novel (E)-N′-(substituted benzylidene)-2(3-oxo-2H-benzo[b][1,4]thiazin-4(3H)-yl)acetohydrazides. Thus, the targeted compounds were successfully synthesized via an easy and general procedure. Hence, 2-aminothiophenol was reacted with maleic anhydride to produce the ester 3,4-dihydro-2-methoxycarbonylmethyl-3-oxo-2H-1,4-benzothiazine. The hydrazinolysis of the obtained ester-based benzothiazinon-3-one was also realized to give the corresponding benzothiazinonic acid hydrazide derivative as a precursor for the synthesis of the desired N˗acylhydrazones, by their condensation with various substituted benzaldehydes. In an attempt to explain the duplication of some peaks observed from the 1H and 13C˗NMR spectral analysis performed on the structures of all newly synthesized N˗acylhydrazones in DMSO˗d6 ; it was concluded that they exist as a mixture of syn˗E and anti˗E diastereoisomers with different isomeric yield ratio. Generally, the results obtained in this study indicate that these N˗acylhydrazones may be envisaged for supplementary structural investigations, and as potential biologically active compounds in diverse applications.

Design, Synthesis, and Antifungal Evaluation of Novel Cuminic Acid Derivatives as Potential Laccase Inhibitors.

In search of novel natural product-based fungicides, 49 cuminic acid derivatives were designed, synthesized, and screened for their in vitro antifungal effects toward seven phytopathogenic fungi and oomycetes. Consequently, several derivatives exhibited strong antifungal activities toward Fusarium graminearum, Botryosphaeria dothidea, and Valsa mali. Among them, compound 2b exhibited the most potent antifungal activity toward B. dothidea (EC50 = 0.96 mg/L), more powerful than chlorothalonil. The in vivo assay against B. dothidea found that the protective and curative effects of 2b were comparable to chlorothalonil. Meanwhile, SEM and TEM observations indicated that 2b could ruin the integrity of mycelial morphology and organelles of B. dothidea. Preliminary mechanism research showed that 2b increased the cell membrane permeability and intracellular ROS level, as well as conspicuously decreased the mycelial dry weight and cell wall chitin contents of B. dothidea. The phytotoxicity test revealed that 2b showed good safety on seeds of mung bean and radish. The in vitro laccase inhibitory activity assay and molecular docking study demonstrated that 2b could be a promising laccase inhibitor. This type of cuminic acid hydrazide derivative would provide valuable inspiration for developing novel fungicides against B. dothidea.

Synthesis, spectroscopic characterization, antimicrobial activity, and computational studies of five and/or six heterocyclic nitrogen rings linked to thienopyrazole moiety

A new series of thienopyrazoles linked to five and/or six heterocyclic nitrogen rings such as pyrazole, triazole-3-thione, oxadiazole, thiazole-2-thione and/or pyrimidone moieties was synthesized starting from 5-amino-1,3-diphenyl-1H-thieno[3,2-c]pyrazole-6-carboxylic acid hydrazide as a key precursor. For the synthesis of new thienopyrazoles 2–13, the carboxylic acid hydrazide derivative 1 served as a crucial intermediary. These novel heterocyclic structures were confirmed by analytical and spectroscopic methods (m.p., IR, 1H NMR, 13C NMR, and MS). The new compounds 2–13 were evaluated for their antimicrobial activity to identify new drug candidates to combat diseases caused by microbial strains. Against numerous bacterial and fungal strains, certain derivatives of the produced compounds 9 and 11 demonstrated impressive antimicrobial activity. Besides, molecular docking of the newly compounds was conducted against methicillin-resistant Staphylococcus aureus (MRSA) (2 × 3f.pdb). Among the series, compounds 9 and 11 exhibited the best binding affinity towards the target enzyme -10.1 and -10.5 kcal/mol, respectively. The optimized structures and molecular orbitals of the best docked compounds were predicted using DFT (Density Functional Theory) analysis. Our findings represented that both derivatives 9 and 11 could be utilized for development antimicrobial drug candidates.

Synthesis of New Heterocyclic Derivatives from 4-(3, 5-Dimethyl-1-phenyl-1H-pyrazol-4-ylazo)- benzoic acid

In this work pyrazolin derivatives were prepared from the diazonium chloride salt of 4-aminobenzoic acid. Azo compounds were prepared from the reaction of an ethanolic solution of sodium acetate and calculated amount of active methylene compound namely, acetyl acetone to obtain the corresponding hydrazono derivative (1). Cyclocondensation reaction of compounds (1) with hydrazine hydrate and phenyl hydrazine in boiling ethanol affording the corresponding pyrazoline-5-one derivatives of 4-aminobenzoic acid (2,3). Then compound (3) was reacted with thionyl chloride to give the corresponding acid chloride derivative(4), followed by conversion into the corresponding acid hydrazide derivative (5) carboxylic acid thiosemicarbazide (11), esters (14,15), thioesters (16,17) and amides (18,19), when treated hydrazine hydrate, thiosemicarbazide, alcohols, alkylthiol and secondary amines in dry refluxing benzene; respectively. Schiff's bases (6-8) were prepared by refluxing of compound (5) with different aldehydes and ketons, then two compounds from the Schiff's bases were cyclized with ?-mercapto acetic acid to give (9 and 10). Furthermore, 1,2,4-triazole derivative (12) have been also prepared by refluxing thiosemicarbazide derivative with sodium hydroxide solution (4%) followed acidification of the result using (10%)hydrolic acid. Moreover, a thiadiazole derivative (13) has been prepared by treatment of thiosemicarbazide derivative with concentrated sulfuric acid as cyclyzing agent. Finally, oxadiazole derivative (20) has prepared by condensation of its acid hydrazide derivative with carbon disulfide in basic medium.

Synthetic Methods and Pharmacological Potentials of Isothiocyanate Derivatives

The present review deals with different synthetic methods of isothiocyanates, including alcohols, aryl chlorides, primary amines, carboxylic acid or carboxylic acid derivatives, cleavage of heterocyclic compounds, and alkene derivatives as a starting material. Furthermore, the thermal rearrangement of thiocyanate, decomposition of thiourea derivatives, and natural isothiocyanates are discussed. It also includes the chemical reaction of isothiocyanates derivatives, such as reaction with alkenes and aromatic compounds, addition of water and amine derivatives, reaction with amino alcohol derivatives, reaction with amino acids and their derivatives, reaction with hydrazine and acid hydrazide derivatives, and miscellaneous reactions. In addition, this review summarizes different pharmaceutical applications of isothiocyanate derivatives, such as anticancer, antimicrobial, antioxidant, and anti-inflammatory activities.

Synthesis and structural characterization of novel di-substituted pyridine-2,6-dicarboxylic acid hydrazide oxo-quinazoline derivative and Cu(II) pincer complex

Crystal and molecular structures of novel pyridine-2,6-dicarboxylic acid (pdc) hydrazide derivative (H2L) dimethanol solvate (H2L = N,N'-bis(2-methyl-4-oxoquinazolin-3(4H)-yl)pyridine-2,6-dicarboxamide) and its copper(II) complex were determined by the single-crystal X-ray diffraction. In the crystal structure, these non-planar molecules form specific cavities that are populated by methanol molecules (held by OH⋯O and NH⋯O hydrogen bonds). Additional stabilization is achieved through a series of offset face-to-face π⋯π interactions between aromatic moieties. The compound is the first structurally described pdc hydrazide derivative containing quinazoline moieties. The reaction of the H2L with copper(II) chloride in methanol resulted in the formation of a new methanol/water solvate containing discrete CuCl2L molecules. Cu(II) ion is coordinated by three nitrogen atoms (two from hydrazide and one from pyridine moieties) in a chelate fashion. Two chloride ions complete distorted square pyramidal coordination geometry. Unlike in H2L molecules, in CuCl2L the hydrazide N-atoms are deprotonated, and coordinated to Cu(II), while quinazoline N-atoms are protonated. In its crystal structure, CuCl2L molecules form dimeric motifs via OH⋯O, NH⋯O, OH⋯Cl hydrogen bond interactions. The adjacent dimers are stacked along the crystallographic b- and c-axis through NH⋯Cl and offset face-to-face π⋯π interactions. The FT-IR spectra analysis indicates a significant shift of CO stretching vibrations of uncoordinated carbonyl groups, that can be attributed to the electron-withdrawing effect of Cu(II) ion. The TG analysis indicates that the weakly bounded solvent molecules evaporate at lower temperatures and that the compound is stable up to 300 °C.

Inhibitions of monoamine oxidases by ferulic acid hydrazide derivatives: synthesis, biochemistry, and computational evaluation

Monoamine oxidases (MAOs) regulate neurotransmitters, and changes in their regulation lead to neurogenerative diseases (NDs). Therefore, MAO inhibitors are used to treat NDs. Ferulic acid, a phenolic compound found in various plant species, has been demonstrated to have a variety of biological functions, including anti-inflammatory, anticancer, and neuroprotective effects. In this study, ten ferulic acid hydrazide derivatives (FA1–FA10) were synthesized, and their ability to inhibit monoamine oxidase (MAO) enzymes was tested. Six candidates demonstrated a more pronounced pattern of inhibitory action against MAO-B than against MAO-A. FA3 had the highest inhibitory efficacy in MAO-B inhibition (IC50 value of 1.88 μM), followed by FA9 (2.08 μM). FA3 has a Ki of 1.92 ± 0.73 μM. A reversibility experiment of MAO-B inhibition by FA3 was conducted using dialysis, and the recovery pattern showed FA3 was a reversible MAO-B inhibitor with a similar recovery to safinamide, a reversible reference inhibitor. These results indicate that FA3 is an effective reversible MAO-B inhibitor. In molecular dynamics and docking, FA3 paired with pi-pi stacking helped stabilize the protein ligand in the active site of MAO-B. According to this study, lead compounds can be used as therapeutic agents to treat neurological conditions, such as Parkinson's disease (PD).

Design, Synthesis, and Biological Evaluation of Novel Camphor-Based Hydrazide and Sulfonamide Derivatives as Laccase Inhibitors against Plant Pathogenic Fungi/Oomycetes.

To discover novel natural product-based fungicidal agrochemicals, 41 novel camphanic acid hydrazide and camphor sulfonamide derivatives were designed, synthesized, and tested for their antifungal profile against four plant pathogenic fungi and three oomycetes. As a result, some derivatives presented pronounced inhibitory activities toward Botryosphaeria dothidea, Fusarium graminearum, Phytophthora capsici, and Phytophthora nicotianae. Especially, compound 4b demonstrated the most potent anti-B. dothidea activity (EC50 = 1.28 mg/L), much stronger than positive control chlorthalonil. The in vivo assay showed that 4b displayed significant protective and curative effects on apple fruits infected by B. dothidea. The primary antifungal mechanism study revealed that 4b could obviously enhance the cell membrane permeability, destroy the mycelial surface morphology and the cell ultrastructure, and reduce the ergosterol and exopolysaccharide contents of B. dothidea. Further, 4b showed potent laccase inhibitory activity in vitro with an IC50 value of 11.3 μM, superior to positive control cysteine. The molecular docking study revealed that 4b could dock well into the active site of laccase by forming multiple interactions with the key residues in the pocket. The acute oral toxicity test in rats presented that 4b had slight toxicity with an LD50 value of 849.1 mg/kg bw (95% confidence limit: 403.9-1785.3 mg/kg bw). This research identified that the camphanic acid hydrazide derivatives could be promising leads for the development of novel laccase-targeting fungicides.

Synthesis, spectroscopic, and lead(II) binding behavior of three novel dibenzo-18-crown-6 hydrazones

Three novel hydrazonic derivatives of dibenzo-18-crown-6 were synthesized and their vibrational and electronic absorption spectroscopic properties thoroughly investigated. Their lead binding behaviors were also characterized and the observations rationalized by density functional theoretical modeling. All three cis-dihydrazonic compounds are of low overall molecular symmetry with their ether cavity adopting an open configuration at the global energy minima where the hydrazonic side-arms are electronically and vibrationally nonequivalent. Their optical absorption features are dominated by π → π * transitions where one side of the molecule exhibits Lewis acid behavior whereas the other behaves like a Lewis base. In addition to their sensitivity to pH, all three derivatives form stable 2:1 metal-ligand complexes with lead, due to coordination at the ether cavity, in addition to the hydrazone “backbone” and possibly the heterocyclic ring. The most stable lead complex is formed with the thiophene carboxylic acid hydrazide derivative due to favorable soft-soft interactions between lead and the ring-based sulfur atom.

Design, synthesis, docking, and antidepressant activity evaluation of isatin derivatives bearing Schiff bases.

Depression is a prevalent psychiatric disorder. Treatment of depression is still a challenge due to the lack of response of some patients to a variety of available medications and side effects. Isatin is an interesting molecule with diversified biological effects. It also participates in many synthetic reactions, as a precursor molecule. In this study, a new series of N-alkyl and N-benzyl isatin derivatives bearing Schiff bases were synthesized and screened for antidepressant activities in mice. The synthesis was initiated by N-alkylation and N-benzylation of isatin by an alkylation reaction to give N-substituted isatins. 2-(Benzyloxy) benzohydrazide derivatives were synthesized by treating methyl2-hydroxybenzoate with benzyl bromide or 4-chlorobenzyl bromide which was followed by a reaction with hydrazine hydrate to provide acid hydrazide derivatives. The final compounds were obtained by condensation of N-substituted isatins with 2-(benzyloxy) benzohydrazide derivatives as Shiff-base products. Compounds were evaluated for antidepressant activities in mice by the locomotor activity, marble burying test, and forced swimming test. Monoamine oxidase-A (MAO-A) enzyme has been used for molecular docking studies. Compounds 8b and 8e in both doses, and 8 c in the lower dose, reduced immobility time during the forced swimming test relative to the control group. All preparations reduced the number of marbles buried compared with the control group. The highest docking score was -11.01 kcal/mol for compound 8e. N-Benzylated-isatin (8b, 8e) and N- acetic acid ethyl ester -isatin derivatives (8c) showed more effective antidepressant activity compared with N-phenyl acetamide isatin derivatives. Docking results relatively confirm the pharmacological results.

Synthesis of N-Mannich bases from 5-((4-methylpiperazin-1-yl)methyl)-1,3,4-oxadiazole-2-thiol

Methyl (4-methylpiperazin-1-yl)acetate (2) were synthesized by the condensation of compound (1) with ethyl bromoacetate in basic media. aThe synthesis of acid hydrazide derivatives (3) was brought about as a result of the reaction between a compound (2) and hydrazine hydrate. In the absence of basic conditions, the reaction of 2-(4-methylpiperazin-1-yl)acetohydrazide (3) with carbon disulfide resulted in the formation of 5-((4-methylpiperazin-1-yl)methyl)-1,3,4-oxadiazole-2-thiol (4). aThe reactions of (4) with different primary and secondary amines in the presence of formaldehyde led to the formation of the corresponding Mannich bases (5a-f).

Thermal properties and processability of modified poly(L-lactide): the role of phenylacetic acid hydrazide derivative

The influence of phenylacetic acid hydrazide (NAPAH) derivative content, melt temperature (170−200°C) and cooling rate (1−20°C/min) on poly (L-lactide) (PLLA) nucleation were investigated. Increasing the content of NAPAH (0.5−3.0 wt.%) had a positive effect on PLLA crystallization, while an increase in the cooling rate and heating temperature had a negative effect. In the case of isothermal crystallization carried out for a long time (180 min), the melting process depended only on the crystallization temperature. NAPAH also influenced the cold crystallization temperature, reduced thermal stability and improved PLLA processability (MFR).

Synthesis, conformational study and DFT analysis of novel nonlinear optically active 2r,6c-diaryl-3t-methylpiperidin-4-one N-(2′-furoyl)hydrazones

A series of nonlinear optical (NLO) active 2-furoic acid hydrazide derivatives, 2r,6c-diaryl-3t-methylpiperidin-4-one N-(2′-furoyl)hydrazones (6–10), were synthesized. The structures of these hydrazones were confirmed unambiguously by Fourier transform infrared spectroscopy, mass spectrometry, elemental analysis, 1H, 13C, HOMO-COSY, HSQC, and HMBC nuclear magnetic resonance spectroscopy. The piperidine core of all the targeted hydrazones (6–10) adopted the chair conformation with the equatorial orientations of all the substituents and the ‘E’ configuration about the C=N bond observed. Density functional theory using the B3LYP/6–31G(d,p) level of theory indicated that all hydrazones favor the ‘E’ isomer state. The Mulliken population, frontier molecular orbitals (FMO), molecular electrostatic potential (MEP) surfaces, and reactivity parameters were also evaluated and showed a good correlation with the experimental data. The efficiency of hydrazones (6–10) in terms of the nonlinear optical (NLO) activity was proven, and the hydrazones (6–10) showed higher NLO activity compared to that of the reference molecule, as determined by the molecular hyperpolarizability measurements. The structural, spectral, and electrochemical properties were also determined, and DFT analysis was consistent with the experimental outcomes. The FMO, MEP, and reactivity parameter analyses revealed intramolecular charge transfer and high reactive features, leading to superior NLO property of hydrazones (6–10).

Synthesis, SAR studies, and insecticidal activities of certain N-heterocycles derived from 3-((2-chloroquinolin-3-yl)methylene)-5-phenylfuran-2(3H)-one against Culex pipiens L. larvae.

An acid hydrazide derivative was synthesized and transformed into a variety of valuable N-heterocycles such as pyridazinone, oxadiazole, triazolopyridazinone, and triazole derivatives via reactions with certain carbon electrophiles such as 4-methoxybenzaldehyde, indole-3-carbaldehyde, pentan-2,4-dione, and carbon disulfide. The chemical structures of all prepared compounds were verified via their analytical and spectroscopic data. The insecticidal activity of the N-heterocycles was evaluated against field and lab strains of the third larval instar of Culex pipiens. All tested compounds exhibited higher larvicidal activity against the lab strains compared to the field strains, with dissimilar ratios. The obtained results demonstrate that the high toxicity achieved by oxadiazole followed the order of furanone, pyridazinone and hydrazide, with lower LC50 values of the hydrazone and N-acetylpyridazinone derivatives compared to that of imidacloprid. Interestingly, these compounds are promising agents for insect pest control, especially since they are insoluble in water and can overcome the disadvantages of neonicotinoid applications in pest management programs.

Copper(Ii) and Zinc(Ii) Complexes of Nicotinic Acid Hydrazide Derivative: Synthesis, Characterization, Density Functional Theory, Anti-Tubercular and Molecular Docking Studies

Copper(Ii) and Zinc(Ii) Complexes of Nicotinic Acid Hydrazide Derivative: Synthesis, Characterization, Density Functional Theory, Anti-Tubercular and Molecular Docking Studies

Synthesis and cytotoxic activity evaluation of some new 1, 3, 4-oxadiazole, 1, 3, 4-thiadiazole and 1, 2, 4- triazole derivatives attached to phthalimide.

Background and purpose:In the last few decades, nitrogen-rich heterocyclic compounds such as 1, 3, 4-thiadiazoles, 1, 2, 4-triazoles and 1, 3, 4-oxadiazoles have received considerable attention because of their notable biological properties, especially cytotoxic effects. The small molecules of mentioned azole derivatives revealed very intensive antitumor activity. In addition, phthalimide-thiadiazole and naphthalimide-triazole hybrid derivatives have shown remarkable cytotoxic effects. According to these observations, some of the hybrid derivatives containing the phthalimide-five-membered azoles were prepared in three steps in this research.Experimental approach:The thiol group of azoles was treated with ethyl chloroacetate which was followed by a reaction with hydrazine hydrate to provide acid hydrazide derivatives. Subsequently, the corresponding acid hydrazides were utilized to prepare the final derivatives through the reaction with phthalic anhydride. Cytotoxic activity of final compounds was evaluated against MCF-7 and HeLa cell lines using MTT assay.Findings/Results:Compound 3d containing two phthalimide moieties in its structure showed a significant improvement in cytotoxic activity with an IC50 value of 29 μM against HeLa cell line. Compounds 3a-3c showed less cytotoxic effects against both cell lines.Conclusion and implications:The combination of the thiadiazole nucleus with two phthalimide structures increased the cytotoxic activity against the HeLa cell line. This increase in cytotoxic activity is probably due to its being more lipophilic characteristic and interaction of this derivative with the biological targets of two directions.

Synthesis and biological evaluation of novel aryloxyacetic acid hydrazide derivatives as anticancer agents

In our continuing search for new anticancer agents, herein we report the synthesis of 2-(4-chloro-3-methylphenoxy)-N'-[(aryl)methylidene]acetohydrazides 3a–j and the evaluation of their anticancer activities on cell viability, morphological changes and caspase-3 activity in cancer cell lines including gastric cancer (MKN45), cervical cancer (HeLa) and breast cancer (MDA-MB-231) cells. 2-(4-chloro-3-methylphenoxy)-N'-[(4-phenylthiophen-2-yl)methylidene] acetohydrazide 3g presented the strongest growth inhibition against MKN45 gastric cancer cell lines with the IC50 value of 1.471 ± 0.23 μM. Moreover, compounds 3b and 3g showed high potency against the HeLa and MDA-MB-231 cell lines having IC50 in the range of 2.38–9.72 μM. These compounds are more selective for the tested human cancer cells than for the mouse fibroblast cell line (NIH/3T3). As a result of the studies conducted in order to understand the molecular mechanism, compounds 3b and 3g enhanced expression of the caspase-3 pro-apoptotic proteins levels besides caspase-3 gene.

Reactivity of 5-phenyl-3-[(2-chloroquinolin-3-yl)methylene] furan-2(3H)-one towards hydrazine and benzylamine: A comparative study

The reactivity of a 2-chloroquinolinylfuranone derivative 3 was investigated against two nitrogen nucleophilic reagents namely, hydrazine and benzylamine. It was found that the regioselectivity of the reaction products was mainly dependent on the nature of nucleophiles, reaction conditions, and solvent used. Therefore, hydrazinolysis of 3 afforded the corresponding acid hydrazide and pyridazinone derivatives depending on the reaction conditions. Otherwise, benzylamine reacted with 3 at different reaction aspects to provide N-benzylamide, N-benzylpyrrolone, and 2-benzylaminoquinolinyl-N-benzylpyrrolone derivatives. The chemical structures of all synthesized compounds were substantiated from their analytical as well as spectroscopic data. Based on the charge density calculations and computational chemical study which excluded the aza-Michael addition reaction and confirm the higher electron-deficiency of lactone carbonyl group than C2-quinoline position, it can be concluded that the C2-furanone becomes more susceptible to attack by the nucleophilic reagent, hydrazine and benzylamine.

Synthesis of some new 4-(2,4-dimethyl-phenyl)-2H-phthalazinone derivatives

Aroylation of m-xylene by phthalic anhydride under Friedel craft’s reaction conditions to afford the corresponding o-aroylbenzoic acid derivative 2, which followed by cyclization reaction with hydroxylamine hydrochloride to produce the correlating benzoxazinone derivative 3, which was utilized as a precursor for the formation of some novel phthalazinone derivatives 4 ˗ 6. This transformation was achieved by interactions with thiosemicarbazide, thiocarbohydrazide, and hydrazine monohydrate and/or ammonium acetate under suitable conditions. 4-Substituted-1(2H)- phthalazinone derivative 6, which undergoes N-alkylation using ethyl bromoacetate to produce the phthalazinone acetic acid ethyl ester derivative 7, that followed by the interaction with hydrazine monohydrate to afford the phthalazinone acetic acid hydrazide derivative 8. The latter product was conducted with different aromatic acid compounds in presence of POCl3, to give the correlating oxadiazoles 9, 10. The chemical structures of all the synthesized compounds are confirmed using physical and spectral data analyses like FT- IR, 1H-NMR, and mass spectroscopy.

Catalytic conversion of 2,4,5-trisubstituted imidazole and 5-substituted 1H-tetrazole derivatives using a new series of half-sandwich (η6-p-cymene)Ruthenium(II) complexes with thiophene-2-carboxylic acid hydrazone ligands

A new series of half-sandwich (η6-p-cymene) ruthenium(II) complexes with thiophene-2-carboxylic acid hydrazide derivatives [Ru(η6-p-cymene)(Cl)(L)] [L = N'-(naphthalen-1-ylmethylene)thiophene-2-carbohydrazide (L1), N'-(anthracen-9-ylmethylene)thiophene-2-carbohydrazide (L2) and N'-(pyren-1-ylmethylene)thiophene-2-carbohydrazide (L3)] were synthesized. The ligand precursors and their Ru(II) complexes (1–3) were structurally characterized by spectral (IR, UV–Vis, NMR and mass spectrometry) and elemental analysis. The molecular structures of the ruthenium(II) complexes 1–3 were determined by single-crystal X-ray diffraction. All complexes were used as catalysts for the one-pot three-component syntheses of 2,4,5-trisubstitued imidazole and 5-substituted 1H-tetrazole derivatives. The catalytic studies optimized parameters as solvent, temperature and catalyst. The catalysts revealed very active for a broad range of aromatic aldehydes presenting either electron attractor or electron donor substituents and, although less active, moderate to high activities were observed for alkyl aldehydes.