Microwave-assisted synthesis,molecular docking and antimicrobial activity of novel 2-(3-aryl,1-phenyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-4-yl)-8<Emphasis Type="Italic">H</Emphasis>-pyrano[2,3-f]chromen-4-ones

An efficient synthetic protocol of microwave-assisted synthesis of some novel 2-(3-aryl,1-phenyl-1H-pyrazol-4-yl)-8H-pyrano[2,3-f]chromen-4-ones 6a–j in excellent yields starting from 3-(3-aryl,1-phenyl-1H-pyrazol-4-yl)-1-(5-hydroxy-2H-chromen-6-yl)-propenones 5a–j was described. This approach offers the advantages of short reaction time (3–5 min), mild reaction conditions, high yields (80–88 %) and convenient operation. All the synthesized compounds were tested in vitro for their antimicrobial activity. The compounds 5h (Ar = 3-ethoxyphenyl), 6c (Ar = 4-chlorophenyl), 6e (Ar = 4-hydroxyphenyl) and 6i (Ar = 3,4-methoxyphenyl) were found to be potent against tested bacterial strains, and compounds 5g (Ar = 4-ethoxyphenyl), 6c (Ar = 4-chlorophenyl) and 6i (Ar = 3,4-methoxyphenyl) were found to be potent against tested fungal strains. The final compounds were subjected to molecular docking studies for the inhibition of enzyme DNA gyrase. The in silico molecular docking results are matching with the in vitro antimicrobial studies, and they may be considered as good inhibitor of DNA gyrase.     

Synthesis,antimicrobial and cytotoxic evaluation of spirooxindole[pyrano-bis-2<Emphasis Type="Italic">H</Emphasis>-l-benzopyrans]

Microwave-assisted tandem double condensation between isatins and 4-hydroxycoumarin under zinc triflate catalysis to afford spirooxindoles in excellent yield is reported. The synthesized compounds were screened for their in vitro antibacterial and antifungal activities. The compounds that showed promising antimicrobial activity (3a, 3j and 3m) were studied for their binding affinity towards AmpC-β-lactamase receptor, which revealed that compound 3a is highly stabilized by strong hydrogen bond interactions with in the binding pocket. The synthesized spirooxindoles were also evaluated for their cytotoxic potential against COLO320 adenocarcinoma colorectal cancer cells. Biological assay and in silico studies indicated compound 3n as the most active in terms of low IC₅₀ value (50.7?μM) and least free energy of binding (?8.89?kcal/mol) respectively.     

Ferrocenyl chalcones with <Emphasis Type="Italic">O</Emphasis>-alkylated vanillins: synthesis,spectral characterization,microbiological evaluation,and single-crystal X-ray analysis

O-alkylated vanillin derivatives 2a–f and acetylferrocene react under Claisen–Schmidt conditions, resulting in good-to-high yields of the corresponding ferrocene chalcones 3a–f. None of the resultant compounds 3b–f has been previously described in the literature. All synthesized compounds were characterized by spectral and physical data, whereas two of them, 1-ferrocenyl-3-(4-ethoxy-3-methoxyphenyl)-prop-2-en-1-one (3b) and 1-ferrocenyl-3-(4-buthoxy-3-methoxy-phenyl)-prop-2-en-1-one (3e), were crystalline substances, suitable for single-crystal X-ray analysis, which confirmed undoubtedly their structures. Chalcones 3a–f were tested for their biological activity and demonstrated relatively good in vitro antimicrobial activity towards different strains of bacteria and fungi. The best antibacterial activity is expressed by compounds 3b and 3c, while compound 3d shows the best antifungal activity.     

Synthesis,characterization and biological evaluation of some novel fluoroquinolones

Different derivatives of fluoroquinolones were synthesized by combining it with different thiadiazoles. The synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance and mass spectral data. The compounds were screened for their antibacterial and antifungal activity. Ciprofloxacin derivatives with thiadiazoles 7c showed good antibacterial as well as antifungal activities, whereas 13c and 13e showed antibacterial and antifungal activity respectively. Sparfloxacin derivative 8c showed both antibacterial and antifungal activity. Sparfloxacin derivatives 14b and 14e showed antibacterial and antifungal activity respectively.     

Synthesis,antibacterial evaluation,and SAR study of some novel 3-aryl/heteroaryl-9-methyl-1,2,4-triazolo-[4,3-<Emphasis Type="Italic">a</Emphasis>]-quinoline derivatives

A series of new quinolin-2-yl moiety linked hydrazones of various aryl/heteroaryl aldehydes has been prepared which on treatment with iodobenzene diacetate in dichloromethane yielded novel triazolo[4,3-a]quinoline derivatives. All the synthesized compounds were characterized on the basis of their FT-IR, ¹H, ¹³C NMR, and mass spectral data. Compounds thus obtained were tested in vitro for their antibacterial activity against three Gram-positive bacterial, namely Enterococcus, Bacillus subtilis, and Staphylococcus aureus, and three Gram-negative bacterial strains, namely Psuedomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae using agar well diffusion method. The percentage similarity of all compounds was also assessed on the basis of physico-chemical and steric parameters as compared to a standard drug, Cefixime using Chem 3D software. Most of the compounds possessed good percentage similarity and exhibited admirable antibacterial activity when compared with the standard drug. Compounds (4a, 4b, 3a, 3c, and 3d) containing pyrazole moiety were found to be most effective against Gram-positive bacteria, S. aureus and B. subtilis.     

New carbodithioate derivatives: synthesis,characterization, and in vitro antibacterial,antifungal, antitubercular,and antimalarial activity

A series of structurally new, 2-(5-substituted-2,3-dioxoindolin-1-yl)ethyl/propyl 4-(3,4-dichlorophenyl)piperazine-1-carbodithioate derivatives 5a–j were designed and synthesized by conventional technique as well as ultrasound irradiation. All the new compounds were characterized by spectral and elemental analyses. Furthermore, they were evaluated for their in vitro antibacterial, antifungal, antitubercular, and antimalarial activities. The results indicated that some of the synthesized compounds posses promising antimicrobial activity against some gram-positive and gram-negative bacteria. Compounds 5b, 5d, and 5e displayed the highest inhibition (99 %) in the range of 3.10–6.25 μg/ml against Mycobacterium tuberculosis H ₃₇ Rv, while compounds 5b–g displayed promising antimalarial activity in the range of 0.043–0.092 μg/mL against Plasmodium falciparum 3D7. Thus, these molecules can provide prospective leads in chemotherapy against tuberculosis and malaria.     

Synthesis of some novel oxazolidinone-thiazole hybrids as potential antimicrobial,antioxidant and UV mediated DNA damage protecting agents

In search of a new class of biologically active agents, some novel oxazolidinone-thiazole hybrids 4a–m have been synthesized and characterized on the basis of a combined use of infrared, NMR (¹H, ¹³C) spectroscopy, mass spectrometry and elemental analysis. All compounds were evaluated for their antimicrobial, antioxidant and ultraviolet mediated DNA damage protective activity. Among the series, compound 4i emerged as the most potent antimicrobial agent, particularly, against Bacillus subtilis, Candida albicans and Saccharomyces cerevisiae in comparison to the standard drugs, Ciprofloxacin (antibacterial) and Amphotericin-B (antifungal). Other promising antimicrobial agents including the compounds 4f–h. In addition, all compounds 4a–m were found to show very high DNA damage protecting ability under ultraviolet irradiation. The antioxidant study revealed that the compounds 4d and 4j were found as the most potent antioxidants as compared to ascorbic acid, a reference compound considered in the study.     

Tyrosinase inhibitory components from the seeds of <Emphasis Type="Italic">Cassia tora</Emphasis>

Ten compounds (1–10) isolated from the seeds of Cassia tora were evaluated for tyrosinase inhibition. Compounds 3, 4, and 7 inhibited tyrosinase enzymatic activity in a dose-dependent manner, with IC₅₀ values of 3.0?±?0.8, 7.0?±?0.4, and 9.2?±?3.4 μM, respectively. Kinetic analyses revealed a mechanism consistent with competitive inhibition. In silico molecular docking showed that compounds 3 and 4 docked in the active site of tyrosinase, whereas 7 interacted with Ala246 and Val248 at outside of the active site, and His244 and Glu256 at inside. Additionally, compounds 3, 4, and 7 suppressed melanogenesis in α-MSH-treated B16F10 melanoma cells at a concentration of 10 μM.     

Linear diarylheptanoids as potential anticancer therapeutics: synthesis,biological evaluation,and structure–activity relationship studies

In efforts to develop effective anticancer therapeutics with greater selectivity toward cancerous cell and reduced side-effects, such as emetic effects due to detrimental action of the drug toward the intestinal flora, a series of linear diarylheptanoids (LDHs) were designed and synthesized in 7 steps with good-to-moderate yields. All synthesized compounds were evaluated for their antibacterial, antiproliferative, and topoisomerase-I and -IIα inhibitory activity. Overall, all compounds showed little to no activity against the bacterial strains tested. Most of the synthesized compounds showed good antiproliferative activity against human breast cancer cell lines (T47D); specifically, the IC₅₀ values of compounds 6a, 6d, 7j, and 7e were 0.09, 0.64, 0.67, and 0.99 μM, respectively. Among the tested compounds, 7b inhibited topo-I by 9.3% (camptothecin 68.8%), 7e and 7h inhibited topo-IIα by 38.4 and 47.4% (etoposide 76.9%), respectively, at the concentration of 100 μM. These results suggest that a set of promising anticancer agents can be obtained by reducing inhibitory actions on different microbes to provide enhanced selectivity against cancerous cells.     

Synthesis,biological evaluation of 2,3-disubstituted-imidazolyl/benzimidazolyl-quinazolin-4(3<Emphasis Type="Italic">H</Emphasis>)-one derivatives

A series of disubstituted-quinazolin-4(3H)-ones derivatives have been synthesized and confirmed through IR, ¹H- and ¹³C-NMR, MS spectroscopy and elemental analysis. Synthesized compounds were screened for in vitro and in vivo anti-inflammatory using human red blood cell membrane stabilization method and carrageenan-induced rat paw edema. The antimicrobial potency was measured by disk diffusion method. The compounds with imidazole (3g) and benzimidazole nucleus (4b and 4f) displayed a significant anti-inflammatory activity by in vitro method. Moreover, the compounds 3d and 4a exhibited a significant anti-inflammatory activity in vivo. The compounds 3d, 3f and 4g were found to be active antimicrobial agents, when compared with reference drug ciprofloxacin and amphotericin B. Thus, these compounds can serve as promising leads for further biological studies.     

Syntheses of arylcinnamic acids,using Alum-Cs<Subscript>2</Subscript>CO<Subscript>3</Subscript> as precursors of new 2-heterostyrylbenzimidazoles and their antimicrobial evaluation

A simple and green methodology has been developed for the syntheses of some new 2-styrylbenzimidazoles. In this method, 2-styrylbenzimidazoles 6(a–x) were synthesized by the condensation of o-phenylenediamines 4(a–c) with cinnamic acids 3(a–h) using glycerol containing boric acid (10 mol%) as the reaction medium at 180 °C about 3–5 h. The cinnamic acids 3(a–h) were obtained by the condensation between aromatic aldehydes 1(a–h), and malonic acid using a new heterogeneous catalytic system such as alum-Cs₂CO₃ in water is described. Compounds 6(a–x) were also obtained alternatively by the condensation of 2-methylbenzimidazoles 5(a-c) with 1(a-h) using the same glycerol containing boric acid (10 mol%) as reaction medium at 180 °C for 5–6 h. The catalytic systems mentioned here were found to be highly active, stable, and recyclable under reaction conditions. All the newly synthesized compounds were characterized by IR, Mass, and NMR spectral analyses. All synthesized compounds were screened for their antimicrobial activity against the clinical strains which include gram-positive bacteria (Micrococcus luteus MTCC 2470, Staphylococcus aureus MTCC 96, Staphylococcus aureus MLS-16 MTCC 2940, Bacillus subtilis MTCC 121) and gram-negative bacteria (Escherichia coli MTCC 739, Pseudomonas aeruginosa MTCC 2453, Klebsiella planticola MTCC 530, and Candida albicans MTCC 3017). The results revealed that compounds (6b, 6g, 6h, 6j, 6k, 6n, 6o, 6t) exhibited significant antibacterial activity almost equal to the standard drug, i.e., Ciprofloxacin.     

Synthesis and antimicrobial evaluation of novel urea derivatives from chromene based oxadiazole amines

A series of novel aryl ureides were synthesized based on oxadiazoles and different substituted aromatic amines. The intermediate amine, (3-(2H-chromen-3-yl)-1,2,4-oxadiazol-5-yl)methanamines (6a) was reacted with aromatic amines in presence of triphosgene to obtain the urea derivatives 7a–d and 7e–i in high yields. The structures of all the intermediates and the final urea derivatives were established by IR, NMR and mass spectrometry data. The antibacterial activity of synthesized compounds was evaluated against two gram-negative bacteria namely Escherichia coli and Pseudomonas aeroginosa and it was observed that the urea derivatives 7a and 7i were promising antibacterial agents.     

Comparative enzyme inhibition study of 1-deazapurines

A series of nitrogen heterocycles including the derivatives of 1-deazapurines, were studied for miscellaneous enzyme inhibition activities in search of the potent enzyme inhibitor. The hyperactive enzymes like carbonic anhydrase-II, phosphodiesterase-I, xanthine oxidase, α-glucosidase, and β-glucuronidase were selected for the study. The compounds 1, 2, 3, 6, 8, 11–13 and 15–17, showed significant and selective activities against different enzymes. The compounds 11 and 12 were found the most potent against carbonic anhydrase-II, α-glucosidase and β-glucuronidase in comparison to their standard compounds. These selective inhibitors can be used as lead compounds for development of drugs against various diseases associated with these enzymes.     

Kinetics and molecular docking of dihydroxanthyletin-type coumarins from <Emphasis Type="Italic">Angelica decursiva</Emphasis> that inhibit cholinesterase and BACE1

In the present study, we investigated the anti-Alzheimer’s disease (AD) potential of six dihydroxanthyletin-type coumarins, 4′-hydroxy Pd–C-III (1), decursidin (2), Pd–C-I (3), 4′-methoxy Pd–C-I (4), Pd–C-II (5), and Pd–C-III (6) from Angelica decursiva by evaluating their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1). Coumarins 1–6 exhibited dose-dependent inhibition of AChE, BChE, and BACE1. IC₅₀ values were 1.0–4.01 µM for AChE, 5.78–13.91 µM for BChE, and 1.99–17.34 µM for BACE1. Kinetic studies revealed that 1 was noncompetitive inhibitor for AChE, while 2–6 were mixed-type inhibitors of AChE. Compounds 1, 5 and 6 had mixed-type inhibitory effects against BChE; 2 was a competitive inhibitor; and 3 and 4 were noncompetitive inhibitors. Against BACE1, compounds 1, 2, 3, 5 showed mixed-type inhibition and 4, 6 were noncompetitive inhibitors. Molecular docking simulation of the compounds demonstrated negative-binding energies indicating high proximity to the active site and tight binding to the enzyme. These data suggested that the compounds inhibited AChE, BChE, and BACE1, providing a preventive and therapeutic strategy for AD treatment.     

Synthesis,antimicrobial and nematicidal evaluation of a new class of triazolo[4,3-<Emphasis Type="Italic">c</Emphasis>]quinazolinylthiazolidinones

In an attempt to find a new class of antimicrobial and nematicidal agents, a series of 2-aryl/heteryl-3-(5-phenyl[1,2,4]triazolo[4,3-c]quinazolin-3-yl)-1,3-thiazolidin-4-ones 5a-k was prepared by one-pot three-component reaction, involving 5-phenyl[1,2,4]triazolo[4,3-c]quinazolin-3-amine 4, aryl/heteroaryl aldehydes and thioglycolic acid, and characterized by physicochemical as well as spectral means. All the newly synthesized compounds 5a–k were tested in vitro for their antimicrobial activity against three representative Gram-positive (Bacillus subtilis, Staphylococcus aureus, Micrococcus luteus), Gram-negative (Proteus vulgaris, Salmonella typhimurium, Escherichia coli) bacteria and four fungal strains (Candida albicans, Aspergillus fumigatus, Trichophyton rubrum, Trichophyton mentagrophytes). These compounds 5a–k, were also evaluated for their nematicidal activity against two nematodes (Ditylenchus myceliophagus, Caenorhabditis elegans). Except phenyl substituted, all the ten aryl/heteroaryl substituted compounds 5b–k showed significant antimicrobial and nematicidal properties against tested microorganisms. Particularly, compounds 5b, 5c, 5g, 5h, 5j and 5k containing electron-withdrawing substituents like chlorophenyl, nitrophenyl, furyl and 1,3-benzodioxole exhibited promising activity comparable to employed standards Ampicillin, Amphotericin B and Levamisole, and emerged as potent antimicrobial and nematicidal agents.     

Synthesis,biological evaluation,and molecular modeling of (<Emphasis Type="Italic">E</Emphasis>)-2-aryl-5-styryl-1,3,4-oxadiazole derivatives as acetylcholine esterase inhibitors

A library of 2,5-disubstituted 1,3,4-oxadiazole derivatives of (E)-2-aryl-5-(3,4,5-trimethoxystyryl)-1,3,4-oxadiazoles 4(a–o) and (E)-2-aryl-5-(2-benzo[d][1,3]dioxol-5-yl)vinyl)-1,3,4-oxadiazoles 5(a–q) were synthesized and evaluated for their in vitro acetylcholinesterase (AChE) inhibitory activity. All the synthesized compounds exhibited moderate to good inhibitory activity toward the AChE enzyme. Among the oxadiazole derivatives examined, compounds 4a, 4g, 5c, and 5m (IC₅₀ values of 24.89, 13.72, 37.65, and 19.63 μM, respectively) were found to be promising inhibitors of AChE. Molecular protein–ligand docking studies were examined for these compounds using GOLD docking software and their binding conformations were determined and the simultaneous interactions mode was also established for the potent derivatives.     

Synthesis of pyridine,pyran and thiazole containing thiophene derivatives and their anti-tumor evaluations

The multi-component reaction of 2-acetylthiophene with aromatic aldehydes and either malononitrile or ethyl cyanoacetate gave the pyran derivatives 4a–4f and pyridine derivatives 5a–5f. On the other hand, the reaction of the 2-acetylthiophene with elemental sulfur and either malononitrile or ethyl cyanoacetate gave the thiophene derivatives 6a and 6b; respectively. Compounds 6a and 6b underwent a series of heterocyclic reactions to give thiazole and thiophene derivatives. All the products were assessed for antitumor activity towards human cancer human gastric cancer (NUGC and HR), human colon cancer (DLD1), human liver cancer (HA22T and HEPG2), human breast cancer (MCF), nasopharyngeal carcinoma (HONE1) cell lines. Compounds 4e, 4f, 5e, 5f, 7b, 8b, 10e, 10f, 11e, 11f, 14d-f, 15d-f, 16a,b and 18b exhibited optimal cytotoxic effect against cancer cell lines, with IC₅₀’s in the nM range. Moreover, 7b, 10e, 14d, 15e and 16b showed no toxicity against shrimp larvae. Anti-proliferative cell activity against cancer cell lines of the most potent compounds showed that compounds 5f and 10e achieved the highest activities among the tested compounds.     

Xanthones from <Emphasis Type="Italic">Garcinia paucinervis</Emphasis> with in vitro anti-proliferative activity against HL-60 cells

Three new xanthones, paucinervins H–J (1–3), as well as eleven known compounds (4–14), were isolated from the leaves of Garcinia paucinervis. The structures of the new compounds (1–3) were elucidated by 1D, 2D NMR spectra and HR ESIMS. In vitro antiproliferative activity against human promyelocytic leukemia HL-60 cells was tested, among which, compounds 2, 5, 6 and 7 exhibited strong growth inhibitory effects with GI₅₀ values ranging from 1.30 to 9.08 μM, respectively. Preliminary SARs were also discussed.     

Microwave assisted synthesis,biological evaluation,and molecular docking of novel chroman scaffolds incorporating spirochromanone framework

A series of novel chroman scaffold incorporate spirochromanone derivatives were synthesized from 2-hydroxyacetophenone and cyclic alkanones under microwave irradiation in good yields. Newly synthesized compounds were characterized by analytical and spectral (IR, proton nuclear magnetic resonance, ¹³C nuclear magnetic resonance, and mass spectrometry) methods. The synthesized compounds were evaluated for their antioxidant and anti-inflammatory activities and were compared with standard drugs. Among all the synthesized compounds 3d (6.09), 3g (5.32), 3h (2.03), 4a (1.17), 4b (0.50), 4c (6.59), 4d (7.86), 4e (6.85), 4f (4.82), and 4g (6.59) were exhibited higher antioxidant activity comparable to that of ascorbic acid (IC₅₀ 8.64?µM). The compounds 3a, 3b, 3c, 4c, and 4d were found to have good anti-inflammatory activity. The binding mode of the titled compounds has been proposed based on the molecular docking studies.     

Synthesis,structures elucidation,DNA-PK,PI3K and antiplatelet activity of a series of novel 7- or 8-(<Emphasis Type="Italic">N</Emphasis>-substituted)-2-morpholino-quinazolines

The DNA-dependent protein kinase and phosphoinositide 3-kinase family is one of the most frequently activated enzymes in a wide range of human cancers; consequently, inhibition of DNA-dependent protein kinase and phosphoinositide 3-kinase represents an approach for cancer therapy. In this work, we have designed and synthesized a series of novel 7- or 8-(N-substituted)-2-morpholino quinazolines 3a–f, 5a–e, 7a–e, and 9 from 7- or 8-amino-2-morpholino quinazolin-4-ones (2a, 4a), the 3-methyl analogues (2b, 4b) and the 4-alkyloxy analogues (6a–b, 8). The compounds were subsequently assayed for DNA-dependent protein kinase and phosphoinositide 3-kinase activity. Most compounds were less active than expected in spite of the strong structural resemblance to the previously studied 7- or 8-(O-substituted)-2-morpholino-1,3-benzoxazine inhibitors. Loss of DNA-dependent protein kinase activity for the quinazolin-4-ones (3a–d and 5a–d) has been attributed to tautomerization to the aromatic enol (4-OH) tautomers. Aromatization of the heterocyclic ring could alter the conformation, and thus binding position, resulting in reduced compound-receptor hydrogen bonding of the morpholine oxygen and 4-carbonyl oxygen. The hetero-aromatic compounds 7a–e and 9 also did not show any DNA-dependent protein kinase activity at 10?µM, which supports the above hypothesis. Compound 7c (R=CH₂(pyridine-4-yl)) displayed selective phosphoinositide 3-kinase delta activity with 80?% inhibition at 10?µM. Similarly, compounds 5a (8-N-substituted, R=CH₂Ph) and 3a (7-N-substituted, R=CH₂Ph) showed selective phosphoinositide 3-kinase beta activity with 69 and 61?% inhibition, respectively. Antiplatelet inhibition assays showed that compound 7e with the 4-O-benzyloxy group and 8-CH₂(pyridine-3-yl) substituents was found to be the most active (IC₅₀ 35?µM).