Synthesis of some novel 1,2,4-triazole and 1,3,4-oxadiazole derivatives of biological interest

In this study, a series of novel [1,2,4]-triazolo-[1,3,4]oxadiazole (8), [1,2,4]-triazolo-[1,3,4]oxadiazole thioethers (9a–b), [1,2,4]-triazolo-[1,3,4]oxadiazole arylidines (10a–g), and bis[1,2,4]-triazole (11) derivatives were prepared with the objective of developing better antimicrobial activity. The structures of the compounds were elucidated by spectral analysis. The newly synthesized compounds (8), (9a–b), (10a–g), and (11) were screened for their antimicrobial activity. Among all the tested compounds (10b) shows significant antibacterial activity.     

Synthesis and biological evaluation of indole containing derivatives of thiosemicarbazide and their cyclic 1,2,4-triazole and 1,3,4-thiadiazole analogs

New indolic derivatives of thiosemicarbazides and some cyclic 1,2,4-triazol-5-thione analogs were synthesized. The newly synthesized compounds as well as some indole containing thiosemicarbazides, 1,2,4-triazoles and 1,3,4- thiadiazoles, which have been reported previously, were investigated for antimicrobial, antifungal and antiphage activity. Certain thiosemicarbazide derivatives and the corresponding cyclic 1,2,4-triazole analogs showed selective antimicrobial or antifungal activity, while they lack any antiphage activity. Antiphage activity was detected for one compound, bearing the 1,3,4-thiadiazole nucleus. The selectively active compounds cover a wide range of lipophilicity. Structure-activity relations show a remarkably similarity in the antimicrobial and antifungal behaviour of the thiosemicarbazides and their cyclic triazo-thien-5-yl analogs, while alpha-naphtyl substitution in the non indolic portion of the molecule is favorable. C5 substitution on the indolic nucleus may also be critical for selective activity.     

Synthesis and biological activity of BIS-1,2,4-triazole and BIS-1,3,4-thiadiazole derivatives

Synthesis of some new 1,2,4-triazole and 1,3,4-thiadiazole derivatives via the condensation of N'-substituted amidrazones and p-phenylenediisothiocyanate (PPD) is presented. The reaction conditions are discussed. Results of a preliminary pharmacological screening are presented.     

Synthesis, structure and biological activity of novel 1,2,4-triazole mannich bases containing a substituted benzylpiperazine moiety

A series of novel Mannich bases with trifluoromethyl-1,2,4-triazole and substituted benzylpiperazine moieties were synthesized. Their structures were confirmed by IR, (1) H NMR and elemental analysis. The single crystal structure of compound 4r was also determined. The preliminary bioassays showed that most of the lead compounds had low herbicidal activity against Brassica campestris, Echinochloa crusgalli, and KARI enzyme. However, most of them exhibited significant fungicidal activity at the dosage of 50 μg/mL toward five test fungi. Among the 18 novel compounds, several showed superiority over the commercial fungicide Triadimefon against Cercospora arachidicola and Fusarium oxysporum f. sp. cucumerinum during this study. Meanwhile, some compounds displayed plant growth regulatory activity at the dosage of 10 μg/mL.     

Antimicrobial activity of Schiff bases of coumarin-incorporated 1,3,4-oxadiazole derivatives: an in vitro evaluation

A series of 3-{5-[(E)-(substituted benzylidene) amino]-1,3,4-oxadiazol-2-yl}-2H-chromen-2-ones (4a–r) were synthesized by the reaction of 3-(5-amino]-1,3,4-oxadiazol-2-yl}-2H-chromen-2-one with different substituted benzaldehydes to form Schiff bases of coumarin-incorporated 1,3,4-oxadiazole derivatives. The structures of the compounds were confirmed on the basis of their elemental analysis and spectral data. The compounds were screened against bacterial strains Staphylococcus aureus NCTC (10418), Escherichia coli NCTC (6571), and fungal strain Candida albicans ATCC (10231). Ciprofloxacin and Ketoconazole were used as standards. The test compounds and standards were evaluated at 100 μg/ml concentration. DMF (N,N-dimethylformamide) was used as solvent and control. Most of the synthesized compounds possess significant antimicrobial activity. Compound (4m) without any substitution of the phenyl ring which is attached to 1,3,4-oxadiazole moiety showed highly significant in vitro growth inhibition against S. aureus and E. coli, while as compound (4g) with para N(CH₃)₂ showed highly significant in vitro growth inhibition against C. albicans.     

Synthesis and biological activities of new Mannich bases of chlorokojic acid derivatives

A novel series of 6-chloromethyl-3-hydroxy-2-substituted 4H-pyran-4-one derivatives were synthesized and tested for their antibacterial, antifungal and antiviral in vitro properties. In the view of activity results, compounds 8–11 (MIC: 8 μg/ml) were more remarkably active against Staphylococcus aureus and Enterococcus faecalis. Compounds 1–7 were highly active against Candida albicans and C. parapsilosis with MIC value of 8 μg/ml. Compound 9 bearing 3-chlorophenyl moiety was determined to be the most active compound against RNA virus PI-3.     

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.     

Non-carboxylic analogues of naproxen: design, synthesis, and pharmacological evaluation of some 1,3,4-oxadiazole/thiadiazole and 1,2,4-triazole derivatives

A series of substituted 1,3,4-oxadiazole (2-7 and 14-19), 1,2,4-triazole (20-25), and 1,3,4-thiadiazole (26-31) derivatives of naproxen have been synthesized by cyclization of 2-(6-methoxy-2-naphthyl)propanoic acid hydrazide 1 and N(1)[2-(6-methoxy-2-naphthyl) propanoyl]-N(4)-alkyl/aryl-thiosemicarbazides (8-13) under various reaction conditions. All the compounds were screened for their anti-inflammatory activity by carrageenan-induced rat paw edema test method. Compounds showing high anti-inflammatory activity were also tested for their analgesic, ulcerogenic, and lipid peroxidation. Few of the synthesized compounds showed significant anti-inflammatory and analgesic activities along with reduced ulcerogenic effect and lipid peroxidation.     

Synthesis and antioxidant activity of new 1,2,4-triazole derivatives

A series of new derivatives of 1,2,4-triazoles have been synthesized and their antioxidant properties have been studied. It was established that the obtained compounds exhibit a stabilizing effect on cell membranes and demonstrate antioxidant activity with respect to erythrocytes under oxidative stress conditions.     

Synthesis and rheological activity of new 1,2,4-triazole derivatives

Reactions of 3,5-dibromo-1,2,4-triazoles containing thietane or thietane-1,1-dioxide with thioglycolic acid yielded 2-[1-(thietanyl-3)-or 2-[1-(1,1-dioxothietanyl-3)-3-bromo-1,2,4-triazolyl-5-thio]acetic acids. Their salts have also been synthesized via reactions with amines and alkalis. Evaluation of the rheological properties showed that some of the synthesized compounds exhibited antiaggregant activity with respect to erythrocytes that was comparable with the effect of pentoxifylline. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 42, No. 9, pp. 15–17, September, 2008.     

Synthesis and anticonvulsant evaluation of semicarbazones of acetophenone Mannich bases

Several semicarbazones of acetophenone and p-chloroacetophenone Mannich bases were designed and synthesized to meet the pharmacophore requirements essential for anticonvulsant activity. Mannich bases of acetophenone and p-chloroacetophenone were prepared by reacting formaldehyde with various secondary amines and then condensed with several aryl semicarbazides to yield the corresponding semicarbazones. All compounds were evaluated for their anticonvulsant activity by maximal electroshock (MES) and by subcutaneous metrazole (ScMet) and strychnine (ScSty) induced seizure methods, and their neurotoxic effects were determined using the rotorod test. The title compounds were also investigated for antidepressant and sedative-hypnotic potentiation properties. It is established that 3-[3-chlorophenyl(β-dimethylaminopropiophenone)semicarbazone] has excellent anticonvulsant activity in MES, ScSty, and ScMet tests and exhibits a potent antidepressant effect in the absence of sedative-hypnotic potentiation. The present study has proved our earlier hypothesis concerning the pharmacophore model with essential binding sites for semicarbazones. The inclusion of an additional moiety (CH₂-CH₂-N<) at the electron donor acceptor group retained the anticonvulsant activity. Published in Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 6, pp. 15–19, June, 2007.     

Synthesis and anti-microbial evaluation of some novel 1,2,4-triazole derivatives

Triazoles with different substituent groups are found to possess diverse applications in the field of medicine and industry. A series of 4-(substituted ethanoyl)amino-3-mercapto-5-(4-nitro)phenyl-1,2,4-triazoles (NU-1 to NU-15) were synthesized as novel antimicrobial agents starting from 4-nitrobenzoic acid. The chemical structures of these newly synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, FAB+ -MS spectral data and elemental analysis. Their antimicrobial activities against Staphylococcus aureus (ATCC-25923), Pseudomonas aeruginosa (ATCC-27853), Escherichia coli (ATCC-8739), Bacillus substilis (ATCC-6633), Candida albicans (MTCC-227), Aspergillus niger (MTCC-3323) and Fusarium oxysporum (MTCC-2087) were investigated.     

Synthesis and pharmacological activities of hydrazones, Schiff and Mannich bases of isatin derivatives

Schiff bases and phenyl hydrazone of isatins were prepared by reacting isatin and the appropriate aromatic primary amine/hydrazines. A new series of the corresponding N-mannich bases were synthesized by reacting them with formaldehyde and diphenylamine. The chemical structures were confirmed by means of their 1H-NMR, IR spectral data and elemental analysis. The compounds were screened for analgesic, antiinflammatory and antipyretic activity. 1-Diphenylaminomethyl-3-(1-naphthylimino)-1,3-dihydroindol-3-one (4), 3-(1-naphthylimino)-5-bromo-1,3-dihydroindol-2-one (2) and 1-diphenylaminomethyl-3-(4-methylphenylimino)-1,3-dihydroindol-3-one (7) were found to exhibit the highest analgesic, anti-inflammatory and antipyretic activity respectively. 1-Diphenylaminomethyl-3-(4-methylphenylimino)-1,3-dihydroindol-3-one (7) was found to be the most active compound of the series.     

Synthesis, antibacterial, antifungal and anti-HIV evaluation of Schiff and Mannich bases of isatin and its derivatives with triazole

Isatin (indole 2,3-dione) and its 5-chloro and 5-bromo derivatives have been reacted with 3-(4'-pyridyl)-4-amino-5-mercapto-4-(H)-1,2,4-triazole to form Schiff bases and the N-Mannich bases of these compounds were synthesised by reacting them with formaldehyde and several secondary amines. Their chemical structures have been confirmed by means of their IR, 1H-NMR data and by elemental analysis. Investigation of antimicrobial activity of compounds was done by agar dilution method against 27 pathogenic bacteria, 8 pathogenic fungi and anti-HIV activity against replication of HIV-1 (III B) in MT-4 cells. Among the compounds tested 1-(piperidinomethyl) 5-bromo 3-[3'-(4"-pyridyl)-5'-mercapto-4'-(H)-1',2',4'-triazol 4'-yl]imino isatin showed the most favourable antimicrobial activity.     

Synthesis and tuberculostatic activity of some (4-phenylpiperazin-1-ylmethyl)-1,3,4-oxadiazole and (4-phenylpiperazin-1-ylmethyl)-1,2,4-triazole derivatives

The phenylpiperazineacetic hydrazide cyclization product. 5-(4-phenylpiperazin-1-ylmethyl)-1,3,4-oxadiazole-2-thiol (1) upon alkylation gave the S-methyl derivative (2). next it was tranmsformed into 1-phenyl-4-(5-pyrrolidin-1-yl-1,3,4-oxadiazol-2-ylmethyl)-piperazine (3). Upon the reaction of I with 1.2-dibromoethane. the derivative (4) containing two joint 1,3,4-oxadiazole systems was obtained. The reactions of compound 1 with chloroacetonitrile and chloroacetic acid gave the corresponding nitrile and carboxylic acid (5, 6) as well. The 4-amino-1,2,4-triazole-3-thiol derivative (7) was obtained in the reaction of compound I with hydrazine hydrate. The phenylpiperazinacetic acid hydrazide was transformed into 1,3,4-oxadiazol-2-ylamine (8), and this, subsequently, into the 2-ethoxy-1,2,4-triazole derivative (9). The compounds obtained were tested in vitro for their tuberculostatic activity. The minimum inhibiting concentrations (MIC) were within 25 - 100 mg/ml.