Superior inhibition of influenza virus hemagglutinin-mediated fusion by indole-substituted spirothiazolidinones.

The influenza virus hemagglutinin (HA) mediates membrane fusion after viral entry by endocytosis. The fusion process requires drastic low pH-induced HA refolding and is prevented by arbidol and tert-butylhydroquinone (TBHQ). We here report a class of superior inhibitors with indole-substituted spirothiazolidinone structure.

Diclofenac-Based Hydrazones and Spirothiazolidinones: Synthesis, Characterization, and Antimicrobial Properties.

We report here the synthesis, structural characterization, and biological evaluation of novel diclofenac-based hydrazone (4a-f) and spirothiazolidinone (5a-f, 6a-f) derivatives designed as potential antimicrobial agents. The compounds were evaluated in vitro for their antiviral activity against a wide spectrum of DNA and RNA viruses. They were further screened in vitro against different strains of bacteria and fungi.

Synthesis and antiviral properties of novel indole-based thiosemicarbazides and 4-thiazolidinones.

A novel series of indolylthiosemicarbazides (6a-6g) and their cyclization products, 4-thiazolidinones (7a-7g), have been designed, synthesized and evaluated, in vitro, for their antiviral activity against a wide range of DNA and RNA viruses. Compounds 6a, 6b, 6c and 6d exhibited notable antiviral activity against Coxsackie B4 virus, at EC50 values ranging from 0.4 to 2.

Indole-based hydrazide-hydrazones and 4-thiazolidinones: synthesis and evaluation as antitubercular and anticancer agents.

A new series of indolylhydrazones (6) and indole-based 4-thiazolidinones (7, 8) have been designed, synthesized and screened for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. 4-Thiazolidinone derivatives 7g-7j, 8g, 8h and 8j displayed notable antituberculosis (anti-TB) activity showing 99% inhibition at MIC values ranging from 6.25 to 25.

N'-(4-Ethyl-cyclo-hexyl-idene)-5-fluoro-3-phenyl-1H-indole-2-carbohydrazide.

The title compound, C23H24FN3O, crystallizes with two independent mol-ecules (I and II) in the asymmetric unit. These pairs of mol-ecules are linked to each other as N-H⋯O dimers with an R 2 (2)(10) motif. Furthermore, the crystal structure also exhibits C-H⋯π inter-actions.

5-Fluoro-N'-(4-methyl-cyclo-hexyl-idene)-3-phenyl-1H-indole-2-carbohydrazide.

The title compound, C22H22FN3O, crystallized with two independent mol-ecules (A and B) in the asymmetric unit; these are linked by a pair of N-H⋯O hydrogen bonds, forming a pseudo-centrosymmetric dimer with an R (2) 2(10) motif. In addition, a number of C-H⋯π inter-actions are also observed. The 1H-indole ring systems in mol-ecules A and B are essentially planar [maximum deviations of 0.

5-Chloro-N'-cyclo-hexyl-idene-3-methyl-1H-indole-2-carbohydrazide.

In the title compound, C16H18ClN3O, the cyclo-hexane ring adopts a distorted chair conformation. In the crystal, pairs of mol-ecules are linked by N-H⋯O hydrogen bonds into inversion dimers, forming R 2 (2)(10) ring motifs. These dimers are connected through C-H⋯N hydrogen bonds into chains along the a axis, forming layers parallel to (101).

Synthesis and evaluation of functionalized indoles as antimycobacterial and anticancer agents.

A new series of 5-fluoro-N(2)-(cyclohexylidene)-3-phenyl-1H-indole-2-carbohydrazides (6a-6e) and their cyclization products 5-fluoro-N-(3-oxo-1-thia-4-azaspiro [4.5]dec-4-yl)-3-phenyl-1H-indole-2-carboxamides (7a-7e, 8a-8e) have been synthesized and evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv using the Microplate Alamar Blue Assay (MABA). Compounds showed moderate to good inhibitory activity at 6.

4'-tert-Butyl-5-chloro-3H-spiro-[1,3-benzothia-zole-2,1'-cyclo-hexa-ne].

In the title compound, C(16)H(22)ClNS, the nine-membered 2,3-dihydro-1,3-benzothia-zole ring system is essentially planar, with a maximum deviation of 0.025 (2) Å for the N atom. Its plane is almost perpendicular to the main plane of the substituted cyclo-hexane ring, which adopts a chair conformation.

5-Chloro-4'-ethyl-3H-spiro-[1,3-benzo-thia-zole-2,1'-cyclo-hexa-ne].

In the title compound, C(14)H(18)ClNS, the 2,3-dihydro-1,3-thia-zole ring adopts an envelope with the S,N-bound C atom at the flap and the cyclo-hexane ring adopts a chair conformation. In the crystal, N-H⋯S hydrogen bonds with C(5) motifs connect the mol-ecules into chains parallel to the c axis.

4-{3-[Hydr-oxy(phen-yl)meth-yl]-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-4-yl}benzene-sulfonamide.

In the title compound, C(15)H(14)N(4)O(3)S(2), the hydr-oxy group is disordered over two positions with occupancies of 0.619 (5) and 0.381 (5).

5-Fluoro-N'-[(E)-4-methoxy-benzyl-idene]-3-phenyl-1H-indole-2-carbohydrazide.

In the title mol-ecule, C(23)H(18)FN(3)O(2), the mean plane of the indole system forms dihedral angles of 44.23 (8) and 14.54 (7)°, respectively, with the phenyl and benzene rings.

2-[2-(2,6-Dichloro-anilino)phen-yl]-N'-(4-propyl-cyclo-hexyl-idene)acetohydrazide.

The asymmetric unit of the title compound, C(23)H(27)Cl(2)N(3)O, contains two crystallographically independent mol-ecules in which the dihedral angles between the benzene rings are 70.1 (3) and 63.8 (3)°.

Synthesis, structure, and antifungal evaluation of some novel 1,2,4-triazolylmercaptoacetylthiosemicarbazide and 1,2,4-triazolylmercaptomethyl-1,3,4-thiadiazole analogs.

Novel 1-[[4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-yl]mercaptoacetyl]-4-alkyl/aryl-3-thiosemicarbazides (5-12) were synthesized by the reaction of 4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-ylmercaptoacetylhydrazide (4) with substituted isothiocyanates. Cyclodehydration of thiosemicarbazides with concentrated sulfuric acid yielded 2-[4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-yl]mercaptomethyl-5-alkyl/arylamino-1,3, 4-thiadiazoles (13-17). The new compounds were evaluated for in vitro antifungal activity using the microdilution method.

N'-[(2Z)-3-Allyl-4-oxo-1,3-thia-zolidin-2-yl-idene]-5-fluoro-3-phenyl-1H-indole-2-carbohydrazide.

In the title compound, C(21)H(17)FN(4)O(2)S, the planar indole fused-ring [maximum deviation 0.009 (1) Å] makes dihedral angles of 54.75 (9) and 14.

Synthesis, characterization and analgesic activity of new 4-arylhydrazono-3-methoxymethyl-2-pyrazolin-5-ones.

New 4-arylhydrazono-3-methoxymethyl-2-pyrazolin-5-ones (5a-j) and 4-arylhydrazono-3-methoxymethyl-1-phenyl-2-pyrazolin-5-ones (6a-j) were synthesized by the reaction of ten novel methyl 2-arylhydrazono-4-methoxy-3-oxobutanoates (4a-j) with hydrazine hydrate and phenylhydrazine, respectively. Treatment of 5a with acetic anhydride yielded 1-acetyl-4-arylhydrazono-3-methoxymethyl-2-pyrazolin-5-one (7). The structures of the tautomerically dynamic compounds were established by spectral data (IR, 1H-NMR, 13C-NMR, EIMS and CIMS) and elemental analysis.

Synthesis and antimicrobial activity of new 6-phenylimidazo[2,1-b]thiazole derivatives.

A series of new N2-substituted-6-phenylimidazo[2,1-b]thiazole-3-acetic acid hydrazides (2a-j) were synthesized and evaluated for in vitro antimicrobial activity against various bacteria and fungi. Some of the compounds showed antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Trichophyton mentagrophytes var. Erinacei NCPF-375, Trichophyton rubrum and Microsporum audounii (MIC 25-0.

Synthesis and preliminary evaluation of new 5-pyrazolinone derivatives as analgesic agents.

New 4-(aroyloxyalkanoyl)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one s (5) were cyclized to 4-(2-aryl-5-unsubstituted/substituted oxazol-4-yl)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-ones (6) employing the Davidson procedure. Preliminary evaluation of analgesic activity revealed that the effect of 4-(2-phenyl-5-ethyloxazol-4-yl)-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one and 4-[2-(4-chlorophenyl)-5-ethyloxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazoline-5-one on acetic acid induced writhing was superior to that of antypyrine and aminopyrine. 4-[2-(4-Chlorophenyl)-5-methyloxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one and 4-[2-(4-methoxyphenyl)-5-ethyloxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one were more potent than aminopyrine, whereas 4-(2-phenyl-5-methyloxazol-4-yl)-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one and 4-[2-(4-methoxyphenyl)-5-methyl-oxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one were not as active (modified Koster's Test; 0.

5-Nitroimidazole derivatives as possible antibacterial and antifungal agents.

Some novel 1-[2-[[5-(2-furanyl)-4-substituted 4H-1,2,4-triazol-3-yl[thio[ethyl[-2-methyl-5-nitro-1H-imidazoles (3), 1-[3-[[5-(2-furanyl/2-thienyl)-4-substituted 4H-1,2,4-triazol-3-yl[-thio]-2-hydroxypropyl[-2-methyl-5-nitro-1H- imidazoles (5) and 1-[3-[(N,N-disubstituted thiocarbamoyl)-thio[-2-hydroxypropyl]-2-methyl-5-nitro-1H-imidazoles (7) were synthesized and evaluated for in vitro antibacterial and antifungal activity. Some of 5 were found to be effective against bacteria and fungi (minimum inhibitory concentration (MIC) 7.3-125 micrograms/ml), whereas 7 were found to be effective against fungi (MIC 3-25 micrograms/ml).

Synthesis and hypnotic activity of new 4-thiazolidinone and 2-thioxo-4,5-imidazolidinedione derivatives.

Conveniently accessible 4-[(2-(3,4-dimethoxyphenyl)ethyl]-3-thiosemicarbazide (2) was converted to new 1-substituted benzylidene/furfurylidene-4- [2-(3,4-dimethoxyphenyl)ethyl]-3-thiosemicarbazides (3) which furnished 2-(substituted benzylidene/furfurylidene) hydrazono-3-[2-(3,4-dimethoxyphenyl)ethyl]thiazolidin-4-ones (4) and 1-(substituted benzylidene/furfurylidene)-amino -3-[2-(3,4-dimethoxyphenyl)ethyl]-2-thioxo-4,5-imidazolidinedio nes (5) on reaction with chloroacetic acid and oxalyl chloride, respectively. The structure of 5 was confirmed by X-ray diffraction studies performed on 5a. 4 and 5 were evaluated for their potentiating effects on pentobarbital induced hypnosis.

Synthesis and anticonvulsant activity of new 3-[(2-furyl)carbonyl]amino-4-thiazolidinone and 2-[(2-furyl)carbonyl]hydrazono-4-thiazoline derivatives.

A series of new 2-aryl-3-[(2-furyl)carbonyl]amino-5-nonsubstituted/methyl-4-thi azolidinones (3) and 2-[(2-furyl)carbonyl]hydrazono-3-alkyl-4-aryl-4-thiazolines (5) was synthesized and evaluated for anticonvulsant activity against pentylenetetrazole induced seizures. Preliminary results indicated that potency was sensitive to substituents at the 2 and 5 positions of the 4-thiazolidinone and 3 and 4 positions of the 4-thiazoline rings. Among 3,2-(phenyl)/ (4-fluorophenyl)-3-[(2-furyl)carbonyl]amino-5-methyl-4-thiazolidinone s (3e and 3f) and among 5, 2-[(2-furyl)carbonyl]hydrazono-3-allyl-4-(4-bromophenyl)-4-thiazol ine (5e), showed the highest protection (40%).

Synthesis and antimicrobial properties of new 4-(alkylidene/arylidene)- amino-5-(2-furanyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones and 6-aryl-3-(2-furanyl)-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines.

A series of 4-(alkylidene/arylidene)amino-5-(2-furanyl)-2,4-dihydro- 3H-1,2,4-triazole-3-thiones (2) and 6-aryl-3-(2-furanyl)-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines (3) were synthesized. The configuration of 2g was assigned on the basis of 1H-NMR data. Of the new derivatives tested, only 2b, 2g, and 4f were found to be active against Staphylococcus aureus and/or Staphylococcus epidermidis (MIC 125-1.

Synthesis and antimicrobial activity of new tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives.

A series of 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thiones was synthesized and evaluated for antibacterial and antifungal activity. All of the tested compounds were found active against Staphylococcus aureus and Staphylococcus epidermidis. The compounds were also active against yeast-like fungi and molds where the anticandidal activity of 3a against Candida albicans was superior to the standards miconazole and clotrimazole.

Synthesis and anticonvulsant activity of new 4-thiazolidone and 4-thiazoline derivatives.

A number of 2-(2-furoylhydrazono)-3-substituted 4-thiazolidone and 2-(2-furoylhydrazono)-3,4-disubstituted 4-thiazoline derivatives were synthesized and evaluated for anticonvulsant activity. Most of the tested compounds showed significant activity against MES induced seizures.