Synthesis and antitumor activity of novel pyridazinone derivatives containing 1,3,4-thiadiazole moiety

Abstract

A series of novel pyridazinone derivatives containing the 1,3,4-thiadiazole moiety were synthesized and characterized by ¹H NMR, 13C NMR, spectroscopies HRMS and IR. Among them, the structure of compound 5c (2-(Tert-butyl)?4-chloro-5-((5-((2-ethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was unambiguously confirmed via single crystal X-ray diffraction analysis. The inhibitory activity of all the target compounds against MGC-803 and Bcap-37 was determined by MTT assay, with doxorubicin (the inhibition rates were 95.5?±?0.4% and 95.7?±?1.0% respectively) as a control. The preliminary results showed that the inhibitory activity of compound 5n (2-(Tert-butyl)?4-chloro-5-((5-((3-fluorophenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was superior to the others. The inhibition rates of MGC-803 and Bcap-37 cells were 86.3?±?2.2% and 92.3?±?0.6% at a concentration of 10?μmol/L, respectively. The preliminary structure-activity relationship showed that when the 2-position of the benzene ring was substituted by a methyl group, such as compound 5j (2-(Tert-butyl)?4-chloro-5-((5-((2,3-dimethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), it exhibited good anticancer activity on MGC-803 cells. Besides, introducing fluorine, chlorine, or trifluoromethyl group onto the benzene ring, such as compound 5?m (2-(Tert-butyl)?4-chloro-5-((5-((4-(trifluoromethoxy)phenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), displayed good anticancer activity on MGC-803 and Bcap-37 cells.     

Synthesis and biological evaluation of some new substituted benzoxazepine and benzothiazepine as antipsychotic as well as anticonvulsant agents

Various 2-((2-((5-benzylideneamino)-1,3,4-oxa/thiadiazol-2-yl)methyl)hydrazinyl) methyl)benzo[b][1,4]oxa/thiazepin-4(5H)-ones (4a–4l), 2-((2-((5-(4-oxo-2-substitutedphenyl thiazolidin-3-yl)-1,3,4-oxa/thiadiazol-2-yl)methyl)hydrazinyl)methyl)benzo [b] [1,4]oxa/thiazepin-4(5H)-ones (5a–5l) and 2-((2-((5-(3-chloro-2-(substitutedphenyl)-4-oxoazetidin-1-yl)-1,3,4-oxa/thia diazol-2-yl)methyl)hydrazinyl)methyl)benzo[b][1,4]oxa/thiazepin-4(5H)-ones (6a–6l) have been synthesized. The structures of these compounds have been established by elemental (C, H, N) and spectral (IR, ¹H-NMR and Mass) analysis. The synthesized compounds were screened for their antipsychotic and anticonvulsant activities. Compound 5l was found to be the most active compound of this series.     

N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)酰胺类新化合物的合成及生物活性

以N-吡啶基吡唑甲酸和2-氨基-3-甲基苯甲酸为起始原料,经由亲核加成、环化和酰化等多步反应合成了一系列结构新颖的N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)酰胺类化合物.测试了所合成化合物的杀虫及抑菌活性,结果表明,新化合物大多化合物在200 mg·L^-1浓度下对东方粘虫(Mythimna separataWalker)具有一定的杀虫活性,尤其是N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)乙酰胺(8a)和N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-3-氯-2,2-二甲基丙酰胺(8e)致死率可达70%;部分化合物在50 mg·L^-1浓度下对油菜菌核病菌的抑菌活性相对较好(54.5%~63.6%),优于triadimefon和chlorantraniliprole;部分化合物如N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-3,3-二甲基丁酰胺80和N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-4-氟苯甲酰胺(8h)对苹果轮纹病菌具有中等抑菌活性.值得注意的是,化合物8e的杀粘虫活性和对油菜菌核病菌的抑菌活性都较为突出,可用作新农药创制研究的新型参考结构.     

Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one containing 4,5-dihydrothiazole-2-thiol derivatives against Meloidogyne incognita

Abstract

A series of novel 1,2,3-benzotriazin-4-one derivatives containing 4,5-dihydrothiazole-2-thiol were synthesized and characterized by ¹H NMR, ¹³C NMR, ¹⁹F NMR and HRMS. The bioassay results showed that compounds 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-7-methoxybenzo[d][1–3]triazin-4(3H)-one, 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-6-nitrobenzo[d][1–3]triazin-4(3H)-one, 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita at the concentration of 10.0?mg L^?1 in vivo. Compound 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one showed excellent nematicidal activity with inhibition 68.3% at a concentration of 1.0?mg L^?1. It suggested that the structure of 1,2,3-benzotriazin-4-one containing 4,5-dihydro-thiazole-2-thiol could be optimized further.     

Synthesis of some novel 3,4,5-trisubstituted triazole derivatives bearing quinoline ring and evaluation of their antimicrobial activity

Abstract

Some new 3,4,5-trisubstituted 1,2,4-triazole derivatives were synthesized and studied for their antimicrobial activity. The lead compounds were obtained starting from 8-hydroxyquinoline and ethyl 2-chloroacetate. The obtained ester compound (1) first reacted with hydrazine hydrate (2) then with phenyl isothiocyanate (3). Ring closure by KOH led to 3-mercapto-1,2,4-triazole derivative (4). Lastly, it reacted with 2-chloro-N-(substituted (benzo)/thiazole)acetamide derivatives to obtain the final compounds (5a–j). The structural elucidation of the compounds was performed by ¹H NMR and ¹³C NMR spectroscopy and high resolution mass spectrometry techniques and elemental analysis. The synthesized compounds were investigated for their antimicrobial activities against seven bacteria and four fungi. As a result of the activity studies, it was observed that compounds N-(6-nitrobenzothiazol-2-yl)-2-[[4-phenyl-5-((quinolin-8-yloxy)methyl)-4H-1,2,4-triazol-3-yl]thio]acetamide (5a) and N-(6-fluorobenzothiazol-2-yl)-2-[[4-phenyl-5-((quinolin-8-yloxy)methyl)-4H-1,2,4-triazol-3-yl]thio]acetamide (5d) were the most active molecules. Also, the antifungal activity of the compounds was found to be higher than their antibacterial activity although lower than the standard drug’s potential. Additionally, the physicochemical properties of the compounds were calculated which were evaluated to be at a suitable range for oral administration.     

Design,synthesis and herbicidal activity of novel cyclic phosphonates with diaryl ethers containing pyrimidine

Abstract

Thirteen novel cyclic phosphates were rationally designed and synthesized by introducing diary ethers containing pyrimidine. All the target compounds were characterized by ¹H, ¹³C, ³¹P NMR and HRMS. The test of herbicidal activity indicated that most of the compounds showed good herbicidal activities against Amaranthus retroflexus. The compounds IA-2 (1-(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)propyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate) and IA-3 ((5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)(phenyl)methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate) exhibited remarkable post-emergency herbicidal activity against the tested monocotyledonous weed at the dosage of 112.5?g ai/ha.     

Synthesis,insecticidal activities,and structure–activity relationships of 1,3,4-oxadiazole-ring-containing pyridylpyrazole-4-carboxamides as novel insecticides of the anthranilic diamide family

The preparation of novel anthranilic diamide derivatives is extremely important for agricultural pest control. In this study, pyridylpyrazole-4-carboxamides containing a 1,3,4-oxadiazole ring were designed and synthesized via the dehydration of aromatic hydrazine derivatives and formanilides in the presence of an alkali. The insecticidal activities of these new compounds against the diamondback moth (Plutella xylostella) were evaluated. N-(4-chloro-2-methyl-6-(5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)phenyl)-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-4-carboxamide ( 8h6 ) showed 67%, 50%, 34%, 20%, and 17% activity at concentrations of 100, 50, 10, 5, and 1 μg ml⁻¹, respectively. Density functional theory calculations showed that the introduction of the 1,3,4-oxadiazole ring significantly changed the electron distributions in both the highest occupied and lowest unoccupied molecular orbitals, resulting in these compounds having much larger energy gaps than the well-known insecticide chlorantraniliprole, which may account for their lower activity. The results of this study demonstrate that anthranilic diamides substituted with a 1,3,4-oxadiazole ring are effective insecticides that can be used for pest management.     

Novel synthesis of isoxazoline indolizine amides for potential application to tropical diseases

Synthetically challenging isoxazoline indolizine amide compounds were designed and prepared for potential application to tropical diseases. Indolizine core structures were synthesized strategically as common intermediates for efficient derivatization. The chemistry for the syntheses of 8-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)indolizine-5-carboxamide (3) and 5-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-indolizine-8-carboxamide (4) is described in this Letter.     

Synthesis,characterization and antibacterial activity of 1-([6-bromo-2-hydroxy-naphthalen-1-yl]arylphenyl)methyl)-3-chloro-4-(arylphenyl)-azetidin-2-one

One-pot synthesis of 1-([6-bromo-2-hydroxy-naphthalen-1-yl]-aryl-phenyl)methyl)-3-chloro-4-(aryl-phenyl)azetidin-2-ones has been reported in the present research work via Staudinger [2 + 2] ketene-imine cycloaddition reaction pathway. The reaction of 1-((Benzylideneamino)(aryl)methyl)-6-bromo-naphthalen-2-ols with chloroacetic acid and triethylamine afforded 1-([6-bromo-2-hydroxynaphthalen-1-yl]aryl-phenyl)methyl)-3-chloro-4-(aryl-phenyl)azetidin-2-ones. For the structural elucidation of series of compounds, different analytical and spectroscopic techniques such as elemental analysis, IR spectra, ¹H-NMR spectra and mass spectra were used. All the newly synthesized compounds were tested for their anti-bacterial activity studies. It revealed that some of the compounds possesses moderate to good activities as compared to standard drugs. The widest spectrum of anti-bacterial activities against both gram-positive and gram-negative bacterial strains among the examined compounds possessed having more hydroxyl group along with β-lactam ring compared to other substituted azetidinones.     

Novel and Efficient Synthesis of 4-Indazolyl-1,3,4-trisubstituted Pyrazole Derivatives

In the present study, 1-(4,5-dihydro-3,6-dimethyl-4-(1,3-diphenyl-1H-pyrazol-4-yl)-3aH-indazol-5-yl)methanone derivatives (9–12) and isoxazoleyl (13–16) have been synthesized by the condensation of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (1–4) with acetyl acetone via Knoevenagel/Michael/aldol reactions in a sequential manner to yield intermediate cyclohexanone (5–8). The intermediates (5–8) treated with NH₂NH₂ · H₂O/NH₂OH · HCl afforded 4-indazolyl-1,3,4-trisubstituted pyrazole and isoxazoleyl derivatives. All of these compounds are reported for the first time, and the structures of these compounds were confirmed by means of infrared, ¹H NMR, ¹³C NMR, and mass spectroscopy.     

Novel imidazole derivatives as antifungal agents: Synthesis,biological evaluation,ADME prediction and molecular docking studies

Abstract

A series of 2-(substituteddithiocarbamoyl)-N-[4-((1H-imidazol-1-yl)methyl)phenyl]acetamide derivatives was designed and synthesized to combat the increasing incidence of drug-resistant fungal infections. All synthesized compounds were characterized by IR, ¹H-NMR, ¹³C-NMR, and HRMS spectra and elemental analyses. Antifungal activity tests were performed against four different fungal strains. Molecular docking studies were performed to investigate the mode of action towards the fungal lanosterol 14α-demethylase, a cytochrome P450-dependent enzyme. ADME studies were carried out and a connection between activities and physicochemical properties of the target compounds was determined. Most of the final compounds exhibited significant activity against Candida albicans and Candida krusei with MIC₅₀ value 12.5?μg/mL. The results of in vitro anti-Candida activity, a docking study and ADME prediction revealed that the newly synthesized compounds have potential anti-Candida activity and evidenced the most active derivative, 5b (2-Pyrrolidinthiocarbonylthio-N-[4-((1H-imidazol-1-yl)methyl)phenyl]acetamide), which can be further optimized as a lead compound.     

Synthesis of novel azabicyclo derivatives containing a thiazole moiety and their biological activity against pine-wood nematodes

Abstract

To explore a new skeleton with nematicidal activity, a series of novel azabicyclo derivatives containing a thiazole moiety were designed, synthesized and evaluated for their nematicidal activities. The bioassay results against pine-wood nematodes (Bursaphelenchus xylophilus) showed that most of the title compounds displayed nematicidal activity at a concentration of 40?mg/L. Especially, the title compounds2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)oxy)-4-(4-chlorophenyl)thiazole (7e), 2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)thio)-4-phenylthiazole (10a) and 2-((8-methyl-8-azabicyclo [3.2.1]octan-3-yl)thio)-4-(4-chlorophenyl)thiazole (10e) exhibited more than 90% mortality against Bursaphelenchus xylophilus.     

Synthesis and Antimicrobial Activity of 2-Substituted-3-((3-(6-Nitrobenzo[D]thiazol-2-yl)-4-oxo-3,4-Dihydroquinazolin-2-yl)Methyl)-1,3,4-thiadiazol-3-ium-5-thiolate

Abstract

A new series of 2-substituted-3-((3-(6-nitrobenzo[d]thiazol-2-yl)-4-oxo-3,4-dihydroquinazolin-2-yl)methyl)-1,3,4-thiadiazol-3-ium-5-thiolate 6(a–j) was synthesized starting from anthranilic acid 1. The structures of the newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, mass spectra, and elemental analysis. The final compounds were tested for their antimicrobial activity against several microbes.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text and tables.]     

Synthesis of new 1,2,3-triazole linked benzimidazole molecules as anti-proliferative agents

One pot click chemistry is used to link triazole and benzimidazole pharmacophore to get N-((1-((1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)aniline and its derivatives. Flexible linkages in the form of –CH₂–R or –O–R/–N–R were designed during synthesis. All the newly synthesized compounds were characterized by FT-IR and NMR spectroscopy as well as high-resolution mass spectrometry. Selected compounds were screened for in vitro anti-proliferative activity using National Cancer Institute (NCI)-60 human tumor cell line screening program. The most potent structure N-((1-((1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)-4-chloroaniline 7e showed 40% growth inhibition in renal cancer cell line (UO-31) at 10?µM concentration.     

Synthesis and in-vitro antioxidant activities of some coumarin derivatives containing 1,2,3-triazole ring

A new green protocol was developed for the S-alkylation of 2-mercapto-1,3,4-oxadiazole by the reaction of 5-substituted-2-mercapto-1,3,4-oxadiazole with propargyl bromide in sodium bicarbonate in water. The newly synthesized 5-[(substitutedphenoxy)methyl]-2-[(prop-2-yn-1-yl)sulfanyl]-1,3,4-oxadiazole when reacted with azidomethyl coumarins underwent regioselective reaction yielding 4-(((4-((5-((substitutedphenoxy)methyl)-1,3,4-oxadiazol-2-yl)sulfanylmethyl)-1H-1,2,3-triazol-1-yl)methyl)-6-methyl)-2H-chromene-2-one or 1-((4-((5-((substitutedphenoxy)methyl)-1,3,4-oxadiazol-2-yl)sulfanylmethy)-1H-1,2,3-triazol-1-yl-)methyl)-3H-benzo[f]chromene-3-one. Structures of the newly synthesized compounds were confirmed by spectral and analytical data. The compounds were screened for their in-vitro antioxidant property.     

New benzimidazole derivatives: Design,synthesis, docking,and biological evaluation

The aim of this study was to synthesize novel enaminonitrile derivatives starting from 2-aminobenzimidazole and utilize this derivative for the preparation of novel heterocyclic compounds and assess their function for biological activity screening. The key precursor N-(1H-benzo[d]imidazol-2-yl)carbonohydrazonoyl dicyanide (2) was prepared in pyridine by coupling of diazotized 2-aminobenzimidazole (1) with malononitrile. Compound 2 was subjected to react with various secondary amines such as piperidine, morpholine, piperazine, diphenylamine, N-methylglucamine, and diethanolamine in boiling ethanol to give the acrylonitriles (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(piperidin-1-yl)acrylonitrile (3), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-morpholinoacrylonitrile (4), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(piperazin-1-yl)acrylonitrile (5), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(diphenylamino)acrylonitrile (6), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(methyl((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)acrylonitrile (7), and (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(bis(2-hydroxyethyl)amino)acrylonitrile (8), respectively. It has been found that the behaviour of nitrile derivative 2 towards hydrazine hydrate to the creation of 4-((1H-benzo[d]imidazol-2-yl)diazenyl)-1H-pyrazole-3,5-diamine (9). The reaction of malononitrile with compound 2 in an ethanolic solution catalyzed with sodium ethoxide afforded 4-amino-1-(1H-benzo[d]imidazol-2-yl)-6-imino-1,6-dihydropyridazine-3,5-dicarbonitrile (11). Moreover, malononitrile reacted with 7 in a boiling ethanolic sodium ethoxide solution to give 2-(5-((1H-benzo[d]imidazol-2-yl)diazenyl)-4-amino-6-(methyl((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)pyrimidin-2-yl)acetonitrile (14). Heating 7 in boiling acetic anhydride and pyridine afforded (2R,3R,4R,5S)-6-(((1E)-2-((1-acetyl-1H-benzo[d]imidazol-2-yl)diazenyl)-1-(N-acetylacetamido)-2-cyanovinyl)(methyl)amino)hexane-1,2,3,4,5-pentayl pentaacetate (15). When compound 15 is heated for a long time in refluxing DMF including a catalytic of TEA, cyclization occurs to give the corresponding (2R,3R,4R,5S)-6-((1-acetyl-3-((1-acetyl-1H-benzo[d]imidazol-2-yl)diazenyl)-4-amino-6-oxo-1,6-dihydropyridin-2-yl)(methyl)amino)hexane-1,2,3,4,5-pentayl pentaacetate (16). In addition, triethyl orthoformate was reacted with compound 7 in the presence of acetic anhydride to afford the corresponding ethoxymethyleneamino derivative (2R,3R,4R,5S)-6-(((1E)-2-((1-acetyl-1H-benzo[d]imidazol-2-yl)diazenyl)-2-cyano-1-(((E) ethoxymethylene)amino)vinyl)(methyl)amino)hexane-1,2,3,4,5-pentayl pentaacetate (17). Also, it has been found that heating a mixture of 7 with DMF/DMA in anhydrous xylene yielded compound (1E)-N'-((1E)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-2-cyano-1-(methyl((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)vinyl)-N,N-dimethylformimidamide (18). In addition, compound 7, when reacted with several acid anhydrides, allowed the matching phthalimide derivatives 19–26. The results showed that compound 14 has significantly higher ABTS and antitumor activities than the other compounds. Molecular modelling was also studied for compounds 22 and 24. The viability of four many cell lines—the African green monkey kidney epithelial cells (VERO), human breast adenocarcinoma cell line (MCF-7), human lung fibroblast cell line (WI-38), and human hepatocellular liver carcinoma cell line (HepG2) was examined to determine the antitumor activities of the newly synthesized compounds. Also, it was found that compounds 9, 11, 15, 16, 22, 23, 24 and 25 are strong against HepG2 cell lines, while 16, 22, and 25 are strong against WI-38 cell lines. Moreover, it was also found that compounds 16 and 22 are strong against VERO cell lines. On the other hand, compounds 7, 14, 15, 16, and 22 are strong while the rest of the other compounds are moderate against the MCF-7 cell line. The result of docking showed that compound 24 got stabilized inside the pocket with a very promising binding score of ? 8.12 through hydrogen bonds with Arg184 and Lys179, respectively.     

Synthesis and insecticidal activities of O,O-dialkyl-2-[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyloxy] (aryl) methylphosphonates

A series of novel O,O-Dialkyl-2-[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyloxy](aryl) methy-lphosphonates I-1–14 were designed and synthesized. The structures of all the title compounds were confirmed by ¹H-NMR, ¹³C-NMR, ³¹P-NMR, IR and elemental analysis. Their insecticidal activities against Mythimna separata and Plutella xylostella were evaluated. The results of bioassays indicated that the title compounds exhibited 20–80% larvicidal activity against Mythimna separata at 1000 mg/L.     

Synthesis and monoamine oxidase A/B inhibitory evaluation of new benzothiazole-thiazolylhydrazine derivatives

Abstract

In this study, a novel series of benzothiazole-thiazolylhydrazine (3a–3i) was synthesized and their structures were characterized by ¹H-NMR, ¹³C-NMR spectrometry, and mass spectroscopy. These compounds were evaluated as inhibitors of type A and type B monoamine oxidase (MAO) enzymes. The most active compound 3b (2-((2-(2-(4-(4-Nitrophenyl)thiazol-2-yl)hydrazineylidene)-2-phenylethyl)thio)benzothiazole) showed strong inhibitory activity at hMAO-A (IC₅₀ of 0.095?±?0.004?µM). Furthermore, compound 3i (2-((2-(2-(4-(2,4-dichlorophenyl)thiazol-2-yl)hydrazineylidene)-2-phenylethyl)thio)benzothiazole) showed significant inhibition profile on hMAO-A with the IC₅₀ values 0.141?±?0.006?µM.     

Design,synthesis, antitubercular and antibacterial activities of pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives and in silico docking studies

Abstract

A novel series pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives have been designed, synthesized and confirmed by FT-IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR, MS, and elemental analysis. The synthesized compounds were screened for their antitubercular activity using microplate alamar blue assay method and antibacterial activity. Among the tested compounds, 4- fluorophenyl (8m), 4- chlorophenyl (8n) and 4-methoxyphenyl (8i) showed potent anti-TB activity (3.12?µg/mL) in comparison with reference drug, Pyrazinamide ((3.12?µg/mL). In addition, all compounds were docked into DprE1 (PDB code: 4KW5) to explore their binding interactions at the active site. The compounds exhibited essential key interactions as that of reported DprE1 inhibitors and hence, the synthesized compounds may be considered as molecular scaffolds for antitubercular activity. Compounds, 4-chlorophenyl (8n) and 4-flurophenyl (8m) showed significant antibacterial activity against Escherichia coli and Staphylococcus aureus strains. In silico prediction of toxicities, druglikeness and drug score profiles of the tested compounds are promising.     

Synthesis and structural elucidation of bioactive triorganotin(IV) derivatives of sodium deoxycholate

Trimethyl (1), tributyl (2), and triphenyl tin (3) derivatives of sodium (R)-4-((3R,5R,8R,9S,10S,12S,13R,14S,17R)-3,12-dihydroxy-10,13-dimethyl-hexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoate (sodium deoxycholate) were synthesized by refluxing sodium deoxycholate with the corresponding triorganotin(IV) chloride in 1?:?1?M ratio. All the three compounds were characterized by elemental analysis, infrared spectroscopy, ¹H, ¹³C, ¹¹⁹Sn NMR, and X-ray diffraction studies. From FT-IR spectra, Δν values proposed bridging or chelating behavior of the ligand. The three compounds gave a trigonal bipyramidal geometry in the solid state and tetrahedral geometry in solution. Single crystal of 1 showed polymeric trigonal bipyramidal geometry. Synthesized compounds obtained were screened for their antimicrobial and antitumor activities against A2780 cell line. Results revealed that only 2 showed significant antibacterial activity. However, all the three compounds exhibited promising antifungal and anticancer activities.