Synthesis, biological evaluation, and molecular modeling studies of novel heterocyclic compounds as anti-proliferative agents

Two novel series of heterocyclic compounds have been synthesized. In first series, isatin was allowed to react with substituted aromatic/cyclic carbonyl compounds to get desired mannich bases (2a–e). In second series, 4,5-disubstituted oxazoles (6a–p) were synthesized. Eight compounds (2c, 6a, 6e, 6f, 6i, 6j, 6m, and 6n) were screened for anticancer activity in 60 cell lines. Compound 2c, 1-[(4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptan-2-yl)methyl]indoline-2,3-dione, showed maximum activity and thus, selected for further evaluation at five dose level screening. Furthermore, molecular docking studies of compounds 2c into the colchicine-binding site of tubulin, revealed possible mode of inhibition by the compound.     

Synthesis and antifungal activity of some new benzimidazole derivatives

Synthesis and antifungal evaluation of 5-ethoxycarbonyl-2-(substituted-benzyl or phenoxymethyl)benzimidazoles are reported. Structures of the compounds were elucidated with IR-, 1H-NMR-, 13C-NMR-, mass-spectra and elemental analysis. Preliminary results show that none of the synthesized benzimidazole derivatives has antifungal activity at the concentration of 100 micrograms/ml against Candida parapsilosis, Candida stellatoidea, and Candida pseudotropicalis.     

Synthesis and pharmacological activity of aroylmethyl derivatives of tricyclic benzimidazole systems containing hydroxy groups in aroyl radicals

The synthesis and pharmacological properties of a series of aroylmethyl derivatives of tricyclic benzimidazole systems containing hydroxy groups in aroyl radicals are described. It is established that most of the synthesized compounds exhibit a high antioxidant activity, possess pronounced hemorheological properties, and influence the blood glucose level. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 3, pp. 9–13, March, 2007.     

Synthesis, pharmacological evaluation and molecular docking studies of indanone derivatives

A new series of isoxazole fused indanones were synthesized form indane-1,3-dione. The newly synthesized derivatives were confirmed by IR, ¹H NMR, and mass spectral data. The synthesized title compounds were evaluated for analgesic, anti-inflammatory, and antimicrobial activities. The modifications carried out in indanone had a positive effect in anti-inflammatory activity when compared to that of other pharmacological activities. The compounds BD ₆ , BD ₇ , BD ₉ , BD ₁₀ , and BD ₁₁ showed good anti-inflammatory activity when compared to that of standard indomethacin. BD ₃ , BD ₄ , and BD ₅ compounds possess moderate anti-inflammatory activity. Some compounds possess moderate analgesic and antimicrobial activity. Docking study reveals that isoxazole nucleus is essential for biological activity. It was concluded that the fusion of isoxazole with indanone nucleus will increase anti-inflammatory activity than analgesic and antimicrobial activity.     

Synthesis and analgesic activity of new pyridine-based heterocyclic derivatives

A series of new heterocyclic derivatives having a pyridine nucleus were synthesized. 4-(5-(2-Chlorophenyl)-4H-1,2,4-triazol-3-yl)pyridine (7c) and 4-(5-(2-Nitrophenyl)-4H-1,2,4-triazol-3-yl)pyridine (7d) presented the best analgesic profie of this series in hot-plate, tail-flick, and formalin-induced licking tests, which was partially prevented by pretreatment with mecamylamine, a nicotinic receptor antagonist.     

New heterocyclic derivatives of benzimidazole with germicidal activity. V. Synthesis and activity of new derivatives of di-2-benzimidazolyl-2,5-furan

In continuation of the research in the field of germicidal and antimycotic agents, the synthesis of 14 new derivatives of di-2-benzimidazolyl-2,5-furan is described. These derivatives are differently substituted (R not equal to R') in the position 5 of the two benzene rings. These new compounds showed no germicidal or fungicidal activity, when tested on different cultures. New compounds are under investigation.     

Synthesis and in-vivo evaluation of carbonyl-amide linkage based new benzimidazole derivatives

In search of pharmacologically active potent compounds, a series of carbonyl-amide linkage based new benzimidazole derivatives were synthesized from acid, aldehydes and isocyanide at ambient temperature via Passerini reaction. All the compounds synthesized were screened for their potential anti-inflammatory, antidiabetic and anticonvulsant properties. The results revealed that compounds 2i and 2j were found to be the most potent anti-inflammatory agents, while compounds 2a, 2c, 2e, 2f, 2i and 2j showed increased antidiabetic activity than the reference drugs and 2a, 2g, 2h, 2i and 2j were found to be the main structural requirement for maintaining anticonvulsant activity.     

Synthesis, molecular modeling, and biological evaluation of 1,2,4-triazole derivatives containing pyridine as potential anti-tumor agents

There is an accumulating body of experimental evidences validating focal adhesion kinase (FAK) as a therapeutic target and offering opportunities for anti-tumor drug development. In present study, we sought to synthesize twenty-eight potential FAK inhibitors as anti-tumor agents based on 1,2,4-triazole skeleton. The bioassay assays demonstrated that compounds 3e and 6j showed the most potent activity, 3e inhibited the growth of HCT116 and HepG2 cell lines with IC₅₀ values of 8.17 and 7.04 μM, while compound 6j showed the most potent biological activity against HCT116 cell line (IC₅₀ = 1.99 μM). Besides, compound 6j also exhibited significant FAK inhibitory activity (IC₅₀ = 2.41 μM). The results of flow cytometry and western-blot assay demonstrated that compounds 3e and 6j possessed good anti-proliferative activity. Docking simulations were performed to position compounds 3e and 6j into the active site of FAK to determine the probable binding model.     

Synthesis, anti-microbial evaluation, and molecular modeling of new pyrazolo[3,4-d]pyrimidine derivatives

Synthesis of some new pyrazolo[3,4-d]pyrimidine derivatives using readily available starting materials are described. A one-pot multi component cyclocondensation reaction was used to prepare the novel 3-methyl-4-aryl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine-6-thiol which served as a new starting material for all new compounds in this research. The anti-microbial activities of the selective synthesized compounds have been evaluated. Some of the newly prepared compounds were found to have moderate to strong anti-microbial activity, e.g., compound 4a, 6a, and 8, in comparison to the reference drugs. Molecular modeling of the most three biologically active new compounds 4a, 6a, and 8 compared to the reference drugs tobramycin and fluconazole was carried out using Fieldalign 2.0 software.     

Synthesis and analgesic activity of new heterocyclic compounds derived from monoterpenoids

A set of new heterocyclic compounds with different types of framework, including a new type of framework, were synthesized by reactions of verbenol epoxide and (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol with aromatic aldehydes containing three methoxy groups. The analgesic activity of these substances was studied. Three compounds possessed considerable activity in vivo in the acetic acid-induced writhing test. (2S,4R,4aR,8S,8aR)-4,7-Dimethyl-2-(2,4,5-trimethoxyphenyl)-3,4,4a,5,8,8a-hexahydro-2H-4,8-epoxychromene exhibited high analgesic activity in both acetic acid-induced writhing and hot plate tests; its selectivity index IS₅₀ exceeded 60.     

Synthesis, antimicrobial and molluscicidal activities of new benzimidazole derivatives

A series of benzimidazole Schiff's bases, thiosemicarbazides were synthesized, azole ring systems as 1,3,4-triazole, 1,3,4-oxadiazole were prepared. 1-Methylbenzimidazole incorporated to substituted dithio-carbamate, thiophenol, diethylamine via acetamido group were synthesized. A series of pyrimidinobenzimidazoles, triazinobenz-imidazoles, and 2-(acetonylamino)-1-methylbenzimidazole were prepared. The antimicrobial and molluscicidal activities of some newly prepared compounds were carried out.     

Synthesis, molecular modeling and anti-inflammatory screening of new 1,2,3-benzotriazinone derivatives

Several new 4(3H)-1,2,3-benzotriazinone derivatives were synthesized and tested for their anti-inflammatory activity and ulcerogenic effect. A docking study on the COX-2 binding pocket has been carried out for the target compounds to rationalize the possible selectivity. Among the tested compounds, the benzotriazinones linked to either thiadiazole (8) or oxadiazole (9) evoked the highest anti-inflammatory activity as well as the best binding profiles into the COX-2 binding site.     

Synthesis, spectral, and antimicrobial evaluation of some new 8-membered phosphorus heterocyclic compounds

Abstract  

Synthesis of 9-substituted-8, 9 10, 11-tetrahydro-7H-7, 11-diaza-9λ⁵-phosphacycloocta [d,e] naphthalene-9-sulfides/selenides (4–13) was accomplished in three steps. 1,8-diamino naphthalene (2) was reacted with tris (bromomethyl) phosphine (1) in the presence of triethylamine in dry tetrahydrofuran (THF) under N₂ atmosphere to form the corresponding intermediate (3). It was converted to the corresponding sulfide (4) and selenide (5) by the reaction with sulfur and selenium, respectively. The intermediates 4 and 5 were reacted with two achiral alcohols and two achiral amines to obtain the title compounds (6–13). The structures of the title compounds were established by elemental analysis and spectral data (IR, ¹H, ¹³C, ³¹P NMR, and FAB mass). The antimicrobial activity of these compounds was evaluated and they exhibited significant activity.