Functionalized 1,4‐Benzothiazine: A Versatile Scaffold with Diverse Biological Properties

1,4‐Benzothiazines are known to represent a class of medicinally important heterocyclic compounds which are extensively used in drug design. They have wide biological properties which qualify them as excellent scaffolds in therapeutic and medicinal research. Thus, many derivatives of this compound have been synthesized as target structures in novel drug development. Hence, the motivation for this present review was the known widespread application of the 1,4‐benzothiazine scaffolds.     

Synthesis of new 3-(substituted phenacyl)-5-[3'-(4H-4-oxo-1-benzopyran-2-yl)-benzylidene]-2,4-thiazolidinediones and their antimicrobial activity

Synthesis of 3-(3-nitrophenacyl)thiazolidine-2,4-dione 2g and 3-(substituted phenacyl)-5-[3'-(4H-4-oxo-1-benzopyran-2-yl)-benzylidene]-2,4-thiazolidinediones 4a-g are reported in this paper. These compounds 4a-g were prepared from 3'-flavone carboxaldehyde and 3-substituted phenacyl-2,4-thiazolidinediones using Knoevenagel reaction. The structures of all compounds were confirmed by IR, 1H-NMR, mass spectral data, and elemental analyses. The molecules 4a-g were evaluated for in-vitro antimicrobial activity against Staphylococcus aureus, Candida albicans, Candida krusei, Candida glabrata, and Candida parapsilosis. Compounds 4c and 4f showed better inhibitory activity when compared to fluconazole against Candida krusei and Candida glabrata.     

Synthesis and antimicrobial evaluation of some novel 2-aminothiazole derivatives of 4-hydroxy-chromene-2-one

Syntheses of 2-aminothiazole derivatives of 4-hydroxy-chromene-2-one 2c-10c are reported in this paper. These compounds 2c-10c were prepared from 3-(2-bromoacetyl)-4-hydroxy-chromene-2-one 1 and corresponding thiourea derivatives 2b-10b using Hantzsch reaction. The structures of all compounds were confirmed by IR and( 1)H-NMR spectroscopy and elemental analyses. The molecules 2c-10c were evaluated for in vitro antimicrobial activity against ten bacteria and twelve fungi. All tested compounds exhibited antibacterial and antifungal activity.     

Activated nitriles in heterocyclic synthesis: Syntheses of thiazole,pyrazole and 4H-1,4-benzothiazine derivatives

4-Arylazo-3-phenyl-5-aminopyrazoles (5a,b) and substituted hydroxythiazoles8a,b were synthesized from the reaction of4a,b with hydrazine hydrate and mercaptoacetic acid respectively. Compounds5a,b and8a,b were also obtained from coupling of2a,b with6 and7, respectively. 4H-1,4-Benzothiazine11 was prepared from1 and10. The reaction of the diazonium salts2a-c with diethyl 3-amino-2-cyanopent-2-en-1,5-dicarboxylate12 was also reported.     

Synthesis of 4-hydroxycoumarin heteroarylhybrids as potential antimicrobial agents

A new series of 4-hydroxycoumarin derivatives 3a-d was synthesized by the reaction of 3-bromo-4-hydroxy coumarin 1 with various heteroaldehydes 2a-d in good yields. The synthesized compounds were characterized on the basis of their elemental and spectral (IR, (1)H-NMR and mass spectrometry) analysis. All target compounds were evaluated for their in-vitro antimicrobial activity against Streptococcus pyogenes, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, and Escherichia coli bacterial strains and fungal cultures of Candida albicans, Aspergillus fumigatus, Trichophyton mentagrophytes, and Penicillium marneffei by disk diffusion assay with slight modifications. The minimum inhibitory concentration (MIC) was determined for the test compounds as well as for reference standards. Among the tested compounds, 3a has shown the most potent antibacterial as well as antifungal activities.     

Synthesis and evaluation of anticonvulsant and antimicrobial activities of 3-hydroxy-6-methyl-2-substituted 4h-pyran-4-one derivatives

In this study, thirteen 3-hydroxy-6-methyl-2-substituted 4H-pyran-4-one derivatives were synthesized for the evaluation of their potential anticonvulsant activity. Mannich bases were prepared by the reaction of substituted piperazine derivatives with allomaltol and formaline. The structures of the synthesized compounds were confirmed by IR, (1)H-NMR and elemental analysis. Their anticonvulsant activities were determined in vivo by maximal electroshock (MES), sub-cutaneous Metrazol (scMet), and rotorod toxicity tests for neurological deficits. The antimicrobial activities of the synthesized compounds were investigated in vitro against some bacteria and fungi using the microdilution broth method. Ac-cording to the activity studies, 3-hydroxy-6-methyl-2-[4-(2-trifluoromethyl-phenyl)-piperazin-1-ylmethyl]-4H-pyran-4-one (3i) was the compound determined to be most active in the scMet test for all doses at four hours and for the 300 mg/kg dose at half an hour. 2-[4-(4-Chloro-phenyl)-piperazin-1-ylmethyl]-3-hydroxy-6-methyl-4H-pyran-4-one (3f) was found to be protective against MES whereas 2-chlorophenyl derivative (3e) was not. Looking at the antifungal activity results, compounds 3b, 3h, and 3i were determined to have activity against all fungi.     

Synthesis and in vitro antimicrobial evaluation of 5-(1-methyl-5-nitro-2-imidazolyl)-4H-1,2,4-triazoles

The increasing clinical importance of drug-resistant pathogens has lent additional urgency to antimicrobial research. Various 5-(1-methyl-5-nitro-2-imidazolyl)-4H-1,2,4-triazoles (4a-6f) were synthesized and tested in vitro for their antibacterial and antifungal activities. Compounds 4a and 4b exhibited significant effects against Bacillus subtilis at MIC ranges of 0.5-1 microg/mL and moderate effects against Staphylococcus aureus.     

2-Amino-3-cyano-4-(5-arylisoxazol-3-yl)-4H-chromenes: synthesis and in vitro cytotoxic activity

A new series of 4-aryl-4H-chromenes bearing a 5-arylisoxazol-3-yl moiety at the C-4 position were prepared as potential anticancer agents. The in vitro cytotoxic activity of the synthesized compounds was investigated against a panel of tumor cell lines including MCF-7 (breast cancer), KB (nasopharyngeal epidermoid carcinoma), Hep-G2 (liver carcinoma), MDA-MB-231 (breast cancer), and SKNMC (human neuroblastoma) using the MTT colorimetric assay. Doxorubicin, a well-known anticancer drug, was used as positive standard drug. Among the synthesized compounds, the 5-(3-methylphenyl)isoxazol-3-yl analog (7j) showed the most potent cytotoxic activity against all five human tumor cell lines.     

Synthesis and antimicrobial activities of N-chloroacetyl-2,6-diarylpiperidin-4-ones

An array of new N-chloroacetyl-2,6-diarylpiperidin-4-ones has been synthesised and their antibacterial activity against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Salmonella typhi, and antifungal activity against Cryptococcus neoformans, Candida albicans, Rhizopus sp., Aspergillus flavus, and Aspergillus niger examined. Compounds 14 against P. aeruginosa, 15 against S. typhi, 16 against S. aureus, and 19 against B. subtilis showed marked antibacterial activity. Similarly, compounds 15 and 19 against A. niger and 19 against A. flavus exerted significant antifungal activities.     

2, 3-Bis(5-alkyl-2-thiono-1, 3, 5-thiadiazin-3-yl) propionic acid: one-pot domino synthesis and antimicrobial activity

In a search for promising antibacterial and antifungal compounds, two new series of 2, 3-bis(5-alkyl-2-thiono-1, 3, 5-thiadiazin-3-yl)propionic acid 1 and their corresponding N, N-dimethylpropionamide 6 have been synthesized. The reaction of 2, 3-diaminopropionate 3, carbon disulfide, formaldehyde, and the appropriate alkyl amines furnished the title compound 1. N, N-dimethylpropionamides 6 were obtained by the reaction of 1 with dimethyl amine in the presence of POCl(3). The newly prepared compounds were screened in vitro against certain strains of Gram-positive and Gram-negative bacteria and compared with nalidixic acid and ciprofloxacin. Moreover, the title compounds were tested for their antifungal activity in vitro against Candida albicans, phytopathogenic, Penicillum expansum and Trichoderma hazianum, and aflatoxin-producing Aspergillus flavus. These compounds exhibit varied activity against the tested pathogenic bacteria and remarkable inhibitory effects on growth or sporulation of some of the tested fungal species.     

Synthesis and potent antimicrobial activity of some novel 4-(5, 6-dichloro-1H-benzimidazol-2-yl)-N-substituted benzamides

A series of 4-(5, 6-dichloro-1H-benzimidazol-2-yl)-N-substituted benzamides were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), methicillin-resistant S. epidermis (MRSE), Enterococcus faecalis, Escherichia coli and Candida albicans. Certain compounds inhibit bacterial growth with low MIC values (microg/mL). Among them, compounds 10 and 11 exhibited the greatest antibacterial activity with MIC values of 3.12 microg/mL against S. aureus, MRSA and MRSE.     

3,4-Disubstituted-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thiones: synthesis, antimicrobial evaluation and QSAR investigations using Hansch analysis

The 3,4-disubstituted-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione derivatives were synthesized and characterized by physicochemical and spectral means, and the results of antimicrobial study of these compounds against Staphylococcus aureus, Escherichia coli, and Candida albicans by tube dilution method indicated that 4-(4-chlorophenyl)-3-(4-nitrophenylsulfonyl)-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione 6 and 4-(4-fluorophenyl)-3-(4-nitrophenylsulfonyl)-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione 12 were the most potential ones. Further, the QSAR studies by Hansch analysis applied to find out the correlation between physicochemical characteristics of synthesized compounds with antimicrobial activity demonstrated the contribution of electronic parameter, total energy (Te) and the topological parameter (valence second order molecular connectivity index (2 chi v). Excellent statistically significant models were developed by Hansch approach (r2 = 0.828-0.898) for the three microorganisms under study. The cross-validated r2 (q2), which is an indication of the predictive capability of the model for all cases was also very good (q2 = 0.776-0.875).     

5-氨基-8-甲氧基喹诺酮类化合物的合成及体内外抗菌作用

通过5-氨基-1-环丙基-6,7-二氟-8-甲氧基-1,4-二氢-4-氧代喹啉-3-羧酸与不同的环胺进行缩合反应,合成了5个未见文献报道的5-氨基-8-甲氧基喹诺酮类化合物。它们的结构均经核磁共振氢谱和高分辨质谱所确证。用环丙沙星及加替沙星作对照,测定了它们的体外抗菌活性,结果表明它们具有广谱活性,其中化合物5、7和9活性十分明显地优于对照药;化合物5和9进一步评价了其体内活性,结果表明化合物5和9分别比对照药加替沙星和莫西沙星具有更优秀的体内活性,值得深入研究。     

Synthesis antimicrobial and antifungal activity of some new 3 substituted derivatives of 4-(2,4-dichlorophenyl)-5-adamantyl-1H-1,2,4-triazole

The synthesis of a series of substituted hydrazones and thiazolidinones is described, starting from N-[4-(2,4-dichlorophenyl)-5-adamantyl-1H-1,2,4-triazol-3-ylmercaptoacetyl]hydrazine. The new compounds were tested for antimicrobial and antifungal activity and some of them exhibited moderate activity against Candida albicans.     

Synthesis and microbiological activity of some novel N-[2-(p-substitutedphenyl)-5-benzoxazolyl]-cyclohexyl carboxamide, -cyclohexyl acetamide and -cyclohexyl propionamide derivatives

The synthesis and microbiological activity of a new series of N-[2-(p-substitutedphenyl)-5-benzoxazolyl]-cyclohexyl carboxamide, -cyclohexyl acetamide and -cyclohexyl propionamide derivatives (4-11) is described. The in vitro microbiological activity of the compounds was determined against gram-positive, gram-negative bacteria and the yeast Candida albicans in comparison with standard drugs. Microbiological results indicated that the synthesized compounds possessed a broad spectrum of activity against the tested microorganisms.     

Synthesis of 2-mercaptobenzimidazole derivatives as potential anti-microbial and cytotoxic agents

A series of novel 2-(1H-benzimidazol-2-ylsulfanyl)-N-(4-oxo-2-phenyl-thiazolidin-3yl)-acetamide 5a-j have been synthesized from various aldehydes and 2-(5-phenyl-[1,3,4]-oxadiazol-2-ylmethylsulfanyl)-1H-benzimidazole 6a-j from various benzoic acids. These compounds were screened for their in-vitro anti-bacterial activity against Staphylococcus aureus and Enterococcus faecalis as Gram positive, Klebsiella pneumoniae and Escherichia coli as Gram negative bacterial strains and for in-vitro anti-fungal activity against Asperigillus fumigatus and Candida albicans. The in vitro cytotoxic properties were studied using brine shrimp bioassay. Results revealed that, compounds 5b, 5d, 5g, 5i, 6b, 6e, 6f, and 6i showed excellent activity against a panel of microorganisms. The cytotoxic activities of 5b, 5g, 5i, 6b, 6f, 6h, and 6i were found to be good. All the newly synthesized compounds were characterized by elemental analysis, IR, (1)H-NMR, (13)C-NMR and MS.     

Convenient synthesis and antimicrobial activity of new 3-substituted 5-(benzofuran-2-yl)-pyrazole derivatives

The reaction of ethyl 4-(benzofuran-2-yl)-2,4-dioxobutanoate 2 with two moles of hydrazine hydrate afforded 5-(benzofuran-2-yl)-1H-pyrazole-3-carbohydrazide 4a, while its reaction with equimolar amount of phenylhydrazine gave ester 3b which then converted to 5-(benzofuran-2-yl)-1-phenyl-1H-pyrazole-3-carbohydrazide 4b. Various new compounds such as imides 5 and 6, acyl hydrazones 7 and 8, bi-pyrazoles 9-12, and 1,3-thiazole derivatives 14 and 15 were prepared from carbohydrazide derivatives 4a, b. The new compounds are tested for their antimicrobial activity. Compounds 2, 5, 7, and 8 showed antifungal activities against C. albicans. Also, compounds 2, 6, 8, and 15 showed antibacterial activities.     

Synthesis, molecular modelling and biological evaluation of 4-amino-2(1H)-quinazolinone and 2,4(1H,3H)-quinazolidone derivatives as antitumor agents

A series of 6-benzoyl-, 6-arylthio- and 6-arylsulfonyl-4-amino-2(1H)-quinazolinones and -2,4(1H,3H)-quinazolinediones were prepared. They were evaluated in vitro for their cytotoxicity against the NCI-60 cancer cell lines.     

Synthesis and biological activity of ethyl 2-(substituted benzylthio)-4-(3'-(ethoxycarbonyl)biphenyl-4-yl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate derivatives

In the present study, a new series of ethyl 2-(substituted benzylthio)-4-(3'-(ethoxycarbonyl)-biphenyl-4-yl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate derivatives was synthesized. The newly synthesized compounds were characterized by (1) H-NMR, mass and C, H, N analyses. All newly synthesized compounds were screened for their antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes and Klebsiella pneumoniae) and antifungal (Aspergillus flavus, Aspergillus fumigatus, Candida albicans, Penicillium marneffei and Trichophyton mentagrophytes) activity. The results revealed that all synthesized compounds have a significant biological activity against the tested microorganisms. Compounds 8a, 8b, 8c, 8e, 8f, 8i, and 8j exhibited good antimicrobial activity.     

Synthesis of 3-(4-substituted benzoylmethyl)-2-benzoxazolinones and screening antimicrobial activities

A number of 3-(4-substituted benzoylmethyl)-2-benzoxazolinones have been synthesized by reacting with 2-benzoxazolinone and 4-substituted phenacyl bromide in ethanol. Their chemical structures were confirmed by IR, 1H NMR and elemental analysis. For screening antimicrobial activity, minimum inhibitory concentration (MIC) values were determined against two Gram positive, one Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus) and three yeast-like the fungi (Candida albicans, Candida krusei, Candida parapsilosis).