Compounds 4a-h Research Articles

Facile One-Pot Conversion of (poly)phenols to Diverse (hetero)aryl Compounds by Suzuki Coupling Reaction: A Modified Approach for the Synthesis of Coumarin- and Equol-Based Compounds as Potential Antioxidants.

A series of 16 (hetero)aryl compounds based on coumarin and equol has been efficiently synthesized by exploring the palladium-catalyzed Suzuki cross-coupling reactions. Polyphenol based on coumarin (4-methyl-7-hydroxy coumarin) was initially converted to corresponding coumarin imidazylate and then subjected to Suzuki coupling reaction with 4-methoxyphenylboronic acid to obtain the coupled product. This modified approach was later developed into a one-pot methodology by directly reacting the polyphenol with 1,1-sulfonyldiimidazole (SDI) and boronic acid in situ to obtain the Suzuki coupled product in one step. Moreover, an array of (poly)phenols based on coumarin and equol were later converted to diverse (hetero)aryl compounds by this optimized step-economic protocol. The synthesized compounds were then subjected to the screening of their potential antioxidant activities by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In our investigation, the compounds 4ah, 4eh, 4gh and 4hh exhibited promising antioxidant potential when compared to the reference standard, butylated hydroxytoluene (BHT). Structure activity relationship (SAR) studies revealed the importance of the presence of electron-donating substituents in enhancing the antioxidant activity of the synthesized compounds.

New Benzimidazole-Triazole Derivatives as Topoisomerase I Inhibitors: Design, Synthesis, Anticancer Screening, and Molecular Modeling Studies.

In this study, we designed, synthesized, and evaluated a series of 1,2,4-triazole benzimidazoles for their cytotoxic effects against the A549, C6, and NIH3T3 cell lines. Additionally, these compounds were assessed for their inhibitory activity against DNA topoisomerase I, aiming to develop novel anticancer agents. The synthesized final compounds 4a-h were characterized using 1H NMR, 13C NMR, and HRMS. Among them, compounds 4b and 4h emerged as the most potent agents against the A549 cell line, exhibiting an IC50 value of 7.34 ± 0.21 μM and 4.56 ± 0.18 μM, respectively. These results were compared to standard drugs, doxorubicin (IC50 = 12.420 ± 0.5 μM) and Hoechst 33342 (IC50 = 0.422 ± 0.02 μM). Notably, all tested compounds displayed higher cytotoxicity toward A549 cells than C6 cells. Compounds 4b and 4h demonstrated significant inhibitory activity against topoisomerase I, highlighting their potential as lead compounds in anticancer therapy. Subsequent in silico molecular docking studies were conducted to elucidate the potential binding interactions of compounds 4b and 4h with the target enzyme topoisomerase I. Molecular dynamics studies also assessed and validated the binding affinity and stability. These studies confirmed the promising binding affinity of these compounds, reinforcing their status as lead candidates. According to DFT, compound 4b having the lower energy gap value (ΔE = 3.598 eV) is more chemically reactive than the others, which is consistent with significant inhibitory activity against topoisomerase I. Furthermore, in silico ADME profiles for compounds 4b and 4h were evaluated using SwissADME, providing insights into their pharmacokinetic properties.

Tandem aqueous extract of onion catalyzed Knoevenagel condensation-Michael addition-cyclization: A green synthesis of 2-amino- 3-cyano-4H-pyran derivatives and their anti-oxidant and molecular docking studies

Aqueous extract of onion catalyzed tandem process incorporating Knoevenagel condensation followed by Michael addition-cyclization is revealed using aldehyde 1, malononitrile 2a and an active methylene compound 3. This method caused diverse 2-amino- 3-cyano-4H-pyran annulated heterocyclic scaffolds in excellent yields (up to 98 %). The synthesized compounds 4ah were also analyzed by single-crystal X-ray diffraction. The reactivity of the active methylene compounds and reasonable mechanism for sequential tandem reactions have been described. Also, this methodology has a simple, easy workup, short reaction time, without column chromatography and eco-friendly reaction conditions. Seventeen out of forty-five synthesized pyran derivatives were screened for their in vitro antioxidant studies. Among the compounds 4ai, 4aj, 4al, 4cd, 4ca, 4cb, 4cc, 4cd have shown excellent and 4aa, 4ac, 4ae, 4ah have exhibited comparable antioxidant activity with ascorbic acid standard. Compounds 4ch-4ck exhibited excellent antioxidant activity than standard. Moreover, mushroom tyrosinase (mh-Tyr) has performed molecular docking properties.

Design, Spectral analysis, DFT calculations, antimicrobial, anti-TB, antioxidant activity and molecular docking studies of novel bis-benzoxazines with cytochrome c peroxidase

We herein report the efficient synthesis of symmetrical bis-benzoxazines by substituted salicylaldehydes and alkyl diamines. The substituted salicylaldehydes (1a-d) and alkyl diamines (2a-b) on reaction synthesize Schiff's bases 3a-h. These compounds on reduction with NaBH4 in dry methanol yielded 2,2′-((alkyl-1,2-diylbis (azanediyl)) bis(methylene))disubstituted phenol, 4a-h in good yield. The preferable 1,2-bis(6-substituted-2H-benzo[e][1,3]oxazin-3(4H)-yl)ethanes, 5a-h formed when the compounds 4a-h undergo an internal Mannich reaction with formaldehyde. Different spectroscopic methods prove the formation of all the compounds. The compounds 3g, 4g, 5c, and 5g showed excellent antibacterial activity against S. aureus, E. coli, S. Typhi, and B. subtilis, antifungal activity against A. flavus, C. Albicans, A. niger, and C. oxysporum with MIC values of 6.25 µg/ml and anti-TB activity against M. tuberculosis for which is equivalent to the standard drug. Furthermore, studies on the antioxidant activity of the compounds 3b, 3c, 3g, 4c, 5b, and 5f revealed that they have excellent antioxidant activity. To comprehend the electronic behavior of compound 5e, Density Functional Theory estimations at the DFT/B3LYP level via 6–31G++ (d, p) replicate the structure and geometry. The first-order hyperpolarizability calculation finds the non-linear visual feature of compound 5e. Finally, HOMO and LUMO analysis were used for the charge transfer interface between the structures. Against Cytochrome c Peroxidase (2 × 08), the compounds 3c and 4c exhibited good docking properties in Molecular docking studies.

Iodine-promoted insertion of the oxygen atom from water in η4-vinylketene[Fe(CO)3] complexes.

Iodine promotes the in situ formation of iron(II) species from η4-vinylketene[Fe(CO)3] (3a-h) as a key intermediate for the synthesis of 2(5H)-furanones (4a-h) by a sequential water-insertion/carbon-oxygen coupling under mild reaction conditions. Compounds 4a-h were obtained in good to excellent yields. A possible reaction pathway was also proposed by DFT calculations. This methodology can be extended to the synthesis of (5H)-pyrrol-2-ones using anilines, with moderate yields and a few limitations.

Access to new Schiff bases tethered with pyrazolopyrimidinone as antibacterial agents: Design and synthesis, molecular docking and DFT analysis

In the present study, a new series of Schiff bases (4a-h) were designed and synthesized via the treatment of the previously prepared 5-aminopyrazolopyrimidinone 3 with a series of differently substituted arylaldehydes. Compound 3 was obtained from the condensation of pyrazolo[3,4-d]pyrimidinone 2 with hydrazine monohydrate. The structures of the newly prepared compounds (4a-h) were confirmed on the basis of their 1H, 13C NMR and ElectroSpray-High Resolution Mass Spectrometry ES-HRMS data. All target compounds were screened in vitro for their antibacterial activity towards three Gram-positive and three Gram-negative strains. The results indiacted that the derivative 4d (R = 4-CH3) exhibited the better inhibitory potential against most bacteria and notably towards B. subtilus and S. aureus with MIC values of 7.60 and 31.25 μg/mL, respectively. Moreover, compound 4c (R = 4-Cl) displayed the highest activity towards Acinitobacter CI with (MIC= 7.81 μg/mL). Besides, molecular docking studies for crystallized structures of the threonine synthase from B. subtilis ATCC 6633 and nucleotidyltransferase (chain A) from P. aeruginosa ATCC 27,853 enzymes highlighted high binding affinity of all synthesized compounds 4 especially ligand 4d and the detected interactions and scoring were found to be in good agreement with the experimental results. Furthermore, The molecular geometry of all derivatives are studied theoretically using the Density Functional Theory (DFT) method with B3LYP/ 6- 311++G(d,p).

Design, synthesis and evaluation of pyrazole bearing α-aminophosphonate derivatives as potential acetylcholinesterase inhibitors against Alzheimer's disease.

A series of novel scaffold of N-substituted pyrazole derived α-aminophosphonates were designed, synthesized and evaluated for their anti-cholinesterase activity. Porcine pancreatic lipase (PPL) was used as a catalyst for the organic transformation. Compounds 4ah and 4bh proved to be more potent than the standard drug tacrine, rivastigmine and galantamine for AChE inhibition activity with IC50 value between 0.055±0.143µM and 0.017±0.02µM respectively. BuChE activity of the synthesized derivatives possessed moderate to weak inhibition potency. 4bhshows a comparable activity to Rivastigmine against BuChE (IC50=6.331±0.17). The compounds did not show any cytotoxicity against HEK-293 cells when compared to standard drugs. Cell viability assay using N2a cell showed compounds 4ah and 4bh showed comparable results to positive control rivastigmine. In addition, these compounds showed promising antioxidant activities against DPPH and H2O2 scavenging. Both 4ah and 4bh showed mixed-type inhibition which supported by molecular docking studies by acting as a dual site inhibitor. The predicted ADME showed good pharmacokinetics as predicted by QikProp. DNA cleavage studies and DNA protection assay of active compounds were also performed. 4bh did not show any damage to DNA and was protective in nature.

Thiolated plastoquinone analogs: Synthesis, characterization, and antimicrobial evaluation

New organic compounds containing quinone moiety continue to be developed and used for a broad spectrum of applications as dyes, drugs, herbicides, fungicides, bactericides, plant-growth regulators, analytical reagents, photoresistors, catalysts, and dehydrogenating agents in organic synthesis. Therefore, in this paper, new plastoquinone analogs possessing arylthio side chain at the 2-position and 2- and 3-positions have been synthesized as possible antibacterial and antifungal agents. Besides single crystal X-ray structural characterization of 3d, 3e, and 4e, the structures of all compounds (3a-h and 4a-h) have been determined based on spectral (IR, 1H NMR, 13C NMR, and mass) data. The current study also contains in vitro antimicrobial screening (using microbroth dilutions method) of synthesized thiolated plastoquinone analogs. The analog containing dimethyl groups within thio moiety (3d) shows moderate antibacterial activity against E. faecalis compared to that of Amikacin. Additionally, the compounds (3d, 3h, and 4f) possessed the activity against S. aureus. 3d was also able to induce appreciable growth inhibitory activity against C. albicans and C. tropicalis with the MIC value of 78.12 μg/mL and 19.53 μg/mL, respectively. This study suggests that four analogs (3d, 3e, 3h, and 4f) could be potential candidates for further development since they show a broad spectrum.

In vitro leishmanicidal activity of lactone 1,4-dihydroquinoline derivatives against Leishmania (Leishmania) amazonensis

A series of lactone 1,4-dihydroquinoline derivatives 4 (4 and 4aa–4cm) was screened for in vitro antileishmanial activity against the promastigote form of Leishmania (Leishmania) amazonensis. Screening results indicate that all of the synthesized compounds significantly reduced the growth of promastigote forms of promastigotes of L. (L.) amazonensis. The cytotoxicity of the most active compounds was also measured on peritoneal macrophage cells. Compounds 4ah and 4bn showed better activities than other derivatives with IC50 values of 6.22 and 9.05 μM, respectively, with selectivity index 22 and 15 times less toxicity to macrophages cells than to parasites, respectively. The experimental data propose that the compounds may be further investigated against amastigote forms and may contribute to the search of new candidates drugs for treatment of cutaneous leishmaniasis.

Design, synthesis, molecular-docking and antimycobacterial evaluation of some novel 1,2,3-triazolyl xanthenones.

As part of an ongoing effort to develop new antitubercular and antimicrobial agents, a series of substituted xanthenone derivatives (7a-p) were synthesized. Xanthenone derivatives (7a-p) were prepared via a one-pot three-component thermal cyclization reaction of β-naphthol (5), substituted 1-aryl-1H-[1,2,3]triazole-4-carbaldehydes (4a-h), and cyclic-1,3-diones (6a, b) in the presence of a catalytic amount of iodine. The newly synthesized compounds were characterized by IR, NMR, mass spectral data, and elemental analysis. These compounds (4a-h and 7a-p) were screened for in vitro antitubercular activity against the M. tuberculosis H37Rv (ATCC 27294) strain, for antibacterial activity against Gram-positive and Gram-negative strains, and for antifungal activity against a pathogenic strain of fungi. Among the compounds tested, most of them showed good to excellent antimicrobial and antitubercular activity. The active compounds displaying good potency in the MTB were further examined for toxicity in a HEK cell line. In addition, the structure and antitubercular activity relationship were further supported by in silico molecular-docking studies of the active compounds against the pantothenate synthetase (PS) enzyme of M. tuberculosis.

Environmentally Benign Synthesis of Tetrahydroindeno[1,2-b]Pyrrole-3-carboxylate Derivatives as Potential Antiinflammatory Agents

A new series of tetrahydroindeno[1,2-b]pyrrole-3-carboxylate derivatives(4) were synthesized by reaction of 5-amino-2-mercapto benzimidazole with 1,3-dicarbonyls and activated carbonyl compounds using ceric ammonium nitrate catalyst by a three component one-pot reaction. Structures of these compounds were established on the basis of infrared spectroscopy, proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, mass spectrometry and elemental analyses. The title compounds 4a-h were evaluated for antiinflammatory activity using the carrageenan-induced paw edema method at a dose of 100 mg/kg in comparison to ibuprofen as a reference drug. Compounds 4a, 4b, 4c and 4d exhibited potent antiinflammatory activity comparable to that of ibuprofen.

2-(chromon-3-yl)imidazole derivatives as potential antimicrobial agents: synthesis, biological evaluation and molecular docking studies.

A series of novel 2-(chromon-3-yl)-4,5-diphenyl-1H-imidazoles (4a-h) were synthesized by one pot condensation of substituted 3-formylchromones (1a-h), benzil (2) and ammonium acetate (3) in refluxing acetic acid at 110 °C under N2 atmosphere. Allylation of compounds 4a-h with allyl bromide in the presence of fused K2CO3 furnished N-allyl-2-(chromon-3-yl)-4,5-diphenyl-1H-imidazoles (6a-h). The synthesized compounds were characterized spectroscopically and evaluated for in vitro antimicrobial activity against various pathogenic bacterial and fungal strains by disc diffusion method. Compounds bearing electron withdrawing substituents such as bromo (4f) showed significant inhibitory activity against S. cerevisiae (MIC 1.4 μg/ml) and 4g containing chloro substituent, displayed more inhibitory potential against C. albicans (MIC 1.5), as compared to the standard drugs. Compounds 6a and 4c exhibit remarkable inhibitory potential against B. subtilis with MIC 0.98 and 1.23, respectively. The time kill assay for active compound 6a was performed by viable cell count (VCC) method to elucidate the microbicidal nature of 2-(chromon-3-yl)imidazoles. A molecular docking study of most active compounds with target 'lanosterol 14α-demethylase' (CYP51) was performed to unravel the mode of antifungal action.

Synthesis and larvicidal and adult topical activity of some hydrazidehydrazone derivatives against Aedes aegypti

A series of novel hydrazide-hydrazone derivatives were synthesized and evaluated for their larvicidal and adult topical activity against Aedes aegypti. The proposed structures of all the synthesized compounds were confirmed using elemental analysis, UV, IR, 1 H-NMR, 13 C-NMR and mass spectroscopy. Compounds 4a-h were screened in larval bioassays at concentrations of 100, 50 and 25 ppm in a dose dependent manner and data for their mortality was recorded. Among the tested compounds, 1-(4-nitrophenyl)-3-(4-{2oxo-2-[2-(2-oxo-1,2-dihydro-3H-ylidene)hydrazinyl] ethyl} phenyl)urea (4b) showed noteworthy larvacidal activity against Aedes aegypti. Dose-response data of compound 4b showed LC 50 and LC 90 values of 30.5 (15.4 – 22.7) and 95.9 (73.8 – 139.4) ppm, respectively. Screening of compounds 4a-h at four doses by topical bioassay indicated a range of activity between 10000 and 1000 ppm.

Anticonvulsant and Antitubercular Activities of 6-Phenyl/Biphenyl-4-yl-2- [2-(pyridin-2-ylamino)-ethyl]- and 6-(Biphenyl-4yl)-2-(2N-subtituted amin- 1-yl)-ethyl derivatives of 4,5-dihydropyridazin-3(2H)-one

Some 6-Phenyl/Biphenyl-4-yl-2-[2-(pyridin-2-ylamino)-ethyl]/-2-(2N-subtituted amin-1-yl)-ethyl-4,5- dihydropyridazin-3(2H)-one (4a-h) were synthesized by reacting 6-phenyl/biphenyl-4,5-dihydropyridazin-3(2H)-one with bromoethyl derivatives of cyclic secondary amines and 2-aminopyridine. All the compounds, 4a-h, were evaluated as anticonvulsant by using maximum electro shock (MES) and isoniazid (INH) induced convulsion methods at 50mg/kg dose level, and as antitubercular by Microplate Almar Blue Assay (MABA) method. In anticonvulsant activity, phenytoin (25mg/kg) and sodium vaproate (50mg/kg) were used as reference drugs. All compounds (4a-h) showed significant anticonvulsant activities against both MES and INH methods, and compound g showed highest activity against MES method. In antitubercular activity, compounds 4c-4h showed 25 μg/ml MIC value, and compounds 4a-4b exhibited 50 µg/ml MIC value when compared with reference drugs [isoniazid (3.125 µg/ml), pyrizinamide (3.125µg/ml)] and (streptomycin 6.25μg/ml) MIC values, and found less potent than the reference drugs. Keywords: Anticonvulsant, Antitubercular, Biological activities, Heterocyclic, Pyridazinone, Synthetic compounds.

Synthesis, characterization and antibacterial activity of new salicylhydrazide containing azopyrazoles

Various ethyl-2-substituted phenyl hydrazono-3-oxobutyrate (2a-h) condensation with 2-hydroxy benzoic acid hydrazide (3) to afford 1-(2-hydroxybenzoyl)-3-methyl-4-(2- substituted phenyl hydrazono)-1H-pyrazol-5(4H)-one (4a-h). The structures of all these compounds (4a-h) were recognized on basis of analytical and spectral data. The newly synthesized compounds were evaluated for their antimicrobial activity against various bacteria and fungi.

Microwave assisted synthesis and antimicrobial evaluation of new fused pyran derivatives bearing 2-morpholinoquinoline nucleus

A new series of fused pyran derivatives 5a-x bearing 2-morpholinoquinoline nucleus has been synthesized under microwave irradiation by a reaction of 2-morpholinoquinoline-3-carbaldehyde 2a-c, malononitrile 3 and compounds 4a-h in presence of NaOH as basic catalyst. All the compounds were screened against three Gram positive bacteria (Streptococcus pneumoniae, Clostridium tetani, Bacillus subtilis), three Gram negative bacteria (Salmonella typhi, Vibrio cholerae, Escherichia coli) and two fungi (Aspergillus fumigatus, Candida albicans) using broth microdilution MIC (Minimum Inhibitory Concentration) method. Of the compounds studied, compounds 5b, 5f, 5k, 5m, 5q, 5s and 5v have found to be most efficient members of the series.

Synthesis of some biologically active 2,4'-bipyridine-5-carbonitriles carrying the 4-hydroxyphenylthio moiety

A series of new 4-aryl-2'-[(4-hydroxyphenyl)thio]-6oxo-1,6-dihydro- 2,4'-bipyridine-5-carbonitriles (3a-k) and 6-amino-4aryl-2'-[(4-hydroxyphenyl) thio]-2,4'-bipyridine-5-carbonitriles (4a-h) were synthesized from 4-hydroxythiophenol (1). The reaction of 4-hydroxythiophenol with 4-acetyl-2-chloropyridine yielded 1-{2-[(4-hydroxyphenyl)thio]pyridin-4-yl}ethanone (2). Further treatment of 2 with ethyl cyanoacetate in the presence of ammonium acetate with various aromatic aldehydes furnished the compounds 3a-k. On the other hand, condensation of 2 with aromatic aldehydes in the presence of alcoholic malononitrile in ammonium acetate gave compounds 4a-h. The structures of the newly synthesized compounds were established on the basis of their elemental analysis, as well as their IR, 1H- and 13C-NMR and mass spectral data. All the title compounds were subjected to in vitro antibacterial testing against two strains and antifungal screening against two fungi. Some of the compounds showed promising activity.

Synthesis and characterizations of some new tetra thiosemicarbazones and their cyclization reactions; tetra 4-methyl-5-etoxycarbonyl-2,3-dihydro-1,3-thiazole and tetra 2-acetylamino-4-acetyl-4,5-dihydro-1,3,4-thiodiazole derivatives

Tetra-aldehyde and ketone derivatives (2a-d) which were used to obtain tetra thiosemicarbazone compounds 3a-h were synthesized via the reaction of Ethene-1,1,2,2,-tetra-yl-tetra-methylenetetra-bromide (1) with aldehydes and ketons. Then, tetra-thiosemicarbazone compounds 3a-h were obtained from the reactions of tetra- aldehyde and keton derivatives (2a-d) with thiosemicarbazite and 4-methyl thiosemicarbazite, respectively. In the same way, tetra-4-methyl5-ethoxycarbonyl-2,3-dihydro-1,3-thiazole compounds 4a-h were synthesized via the reaction of tetra-thiosemicarbazone compounds 3a-h with ethyl-2-chloroacetoacetate. Then, tetrathiosemicarbazone compounds 3a-h were reacted with acetic anhydride, and yielded tetra-2acetyl-amino-4-acetyl-4,5-dihydro-1,3,4-thiodiazol compounds (5a,b,c,e,f,g). They were characterized by elemental analysis, infrared, 1 H and 13 C-NMR, mass spectroscopy. Then, the microbial features of all compounds were studied by the known method.

Synthesis and antimicrobial screening of 5-arylidene-2-imino-4-thiazolidinones

The condensation of 2-aminobenzothiazole-6-carboxylic acid (1) with chloroacetyl chloride in refluxing chloroform in the presence of anhydrous K2CO3 gives 2-(2- chloroacetylamino)benzothiazole-6-carboxylic acid (2). Compound (2) on treatment with KSCN in refluxing acetone yields 2-(2-imino-4-oxo-thiazolidin-3-yl)benzothiazole-6-carboxylic acid (3). Compound (3) on condensation with various aromatic aldehydes affords a series of 2-(5- (arylidene)-2-imino-4-oxo-thiazolidin-3-yl)benzothiazole-6-carboxylic acid (4a-h). The synthesized compounds (4a-h) are screened for their antibacterial as well as antifungal activity. All the tested compounds show slight to moderate activity against the selected microorganisms.

Synthesis and Biological Activity of N-Substituted-3-chloro-2-azetidinones

2-Aminobenzothiazole-6-carboxylic acid (1), on condensation with chloroacetyl chloride yielded 2-(2-chloroacetylamino)benzothiazole-6-carboxylic acid (2), which on amination with hydrazine hydrate yielded in turn 2-(2-hydrazinoacetylamino)benzo-thiazole-6-carboxylic acid (3). Compound 3, on condensation with various aromatic aldehydes afforded a series of 2-{2-[N'-(arylidene)hydrazino]acetylamino}benzothiazole-6-carboxylic acids 4a-h, which upon dehydrative annulation in the presence of chloroacetyl chloride and triethylamine yielded 2-{2-[3-chloro-2-(aryl)-4-oxoazetidin-1-ylamino]-acetylamino}benzothiazole-6-carboxylic acids 5a-h. The synthesized compounds 4a-h and 5a-h were screened for their antibacterial activity against four microorganisms: Staphylococcus aureus (Gram positive), Bacillus subtilis (Gram positive), Psuedomonas aeruginosa (Gram negative) and Escherichia coli (Gram negative). They were found to exhibit good to moderate antibacterial activity. The antifungal activity of these compounds were also tested against three different fungal species. None of them were active against the species tested.