Nida Ambreen

Schiff bases of 3-formylchromone as thymidine phosphorylase inhibitors.

3-Formylchromone (1), 3-methyl-7-hydroxychromone (2) and Schiff bases of 3-formylchromone 3-19 have been synthesized and their anti-thymidine phosphorylase inhibitory activity was evaluated. Compounds 1-19 showed a varying degree of thymidine phosphorylase inhibition with IC(50) values 19.77+/-3.25 to 480.21+/-2.34 microM. Their activity was compared with the standard 7-deazaxanthine (IC(50)=39.28+/-0.76 microM). Compound 12 showed an excellent thymidine phosphorylase inhibitory activity with an IC(50) value of 19.77+/-3.25 microM, better than the standard. Compound 4 also showed an excellent inhibitory activity (IC(50)=40.29+/-4.56 microM). The parent 3-formylchromone (1) and 3-methyl-7-hydroxychromone (2) were found to be inactive. The structures of the compounds were elucidated by using spectroscopic techniques, including (1)H NMR, EI MS, IR, UV and elemental analysis.

3-Formylchromones: Potential antiinflammatory agents

The synthesis and characterization of 3-formylchromone (1) and its derivatives 2-24 and evaluation of their potential antiinflammatory activities is reported here. These compounds were characterized by (1)H NMR, EI MS, IR, and UV spectroscopic techniques and elemental analysis. The synthesized compounds were evaluated by using various in vitro and in vivo assay models for antiinflammatory activity and their effects were compared with known standard drug such as aspirin and indomethacin. Among all tested compounds, 1, 2, 5, 6, 9, 14, 16-19, 21-23, showed promising antiinflammatory activities. The results and SAR has been discussed in this report.

Evaluation of bisindole as potent β-glucuronidase inhibitors: Synthesis and in silico based studies

Bisindole analogs 1-17 were synthesized and evaluated for their in vitro β-glucuronidase inhibitory potential. Out of seventeen compounds, the analog 1 (IC50=1.62±0.04 μM), 6 (IC50=1.86±0.05 μM), 10 (IC50=2.80±0.29 μM), 9 (IC50=3.10±0.28 μM), 14 (IC50=4.30±0.08 μM), 2 (IC50=18.40±0.09 μM), 19 (IC50=19.90±1.05 μM), 4 (IC50=20.90±0.62 μM), 7 (IC50=21.50±0.77 μM), and 3 (IC50=22.30±0.02 μM) showed superior β-glucuronidase inhibitory activity than the standard (d-saccharic acid 1,4-lactone, IC50=48.40±1.25 μM). In addition, molecular docking studies were performed to investigate the binding interactions of bisindole derivatives with the enzyme. This study has identified a new class of potent β-glucouronidase inhibitors.

2,4,6-Trichlorophenylhydrazine Schiff Bases as DPPH Radical and Super Oxide Anion Scavengers

Syntheses of thirty 2,4,6-trichlorophenylhydrazine Schiff bases 1-30 were carried out and evaluated for their in vitro DPPH radical and super oxide anion scavenging activities. Compounds 1-30 have shown a varying degree of DPPH radical scavenging activity and their IC50 values range between 4.05-369.30 µM. The compounds 17, 28, 18, 14, 8, 15, 12, 2, 29, and 7 exhibited IC50 values ranging between 4.05±0.06-24.42±0.86 µM which are superior to standard n-propylgallate (IC50=30.12±0.27 µM). Selected compounds have shown a varying degree of superoxide anion radical scavenger activity and their IC50 values range between 91.23-406.90 µM. The compounds 28, 8, 17, 15, and 14, showed IC50 values between 91.23±1.2-105.31±2.29 µM which are superior to standard n-propylgallate (IC50=106.34±1.6 µM).

1,3,4-Oxadiazole-2(3H)-thione and its analogues: a new class of non-competitive nucleotide pyrophosphatases/phosphodiesterases 1 inhibitors.

A series of 1,3,4-oxadiazole-2 (3H)-thiones and 1,3,4-thiadiazole-2 (3H)-thiones were synthesized and evaluated for their inhibitory activities against the two nucleotide pyrophosphatase phosphodiesterase 1 enzymes. Dixon, as well as Lineweaver-Burk plots, and their secondary replots have indicated that the inhibition was of pure non-competitive type, against both snake venom and pure human recombinant enzymes as the V(max) values decreases without affecting the K(m) values. 5-[4-(t-Butyldimethylsilyloxy)-phenyl]-1,3,4-thiadiazole-2 (3H)-thione (17) and [4-(t-butyldimethylsilyloxy)-phenyl]-1,3,4-oxadiazole-2 (3H)-thione (1) were found to be the most active compounds with IC(50) values 66.47 and 368microM, respectively. The K(i) values were 100microM and 360microM against the snake venom and human recombinant NPP1 enzyme, respectively. Most active compounds were found to be non-toxic in neutrophil viability assay.

Phenoxyacetohydrazide Schiff bases: β-glucuronidase inhibitors.

Phenoxyacetohydrazide Schiff base analogs 1–28 have been synthesized and their in vitro β-glucouoronidase inhibition potential studied. Compounds 1 (IC50 = 9.20 ± 0.32 µM), 5 (IC50 = 9.47 ± 0.16 µM), 7 (IC50 = 14.7 ± 0.19 µM), 8 (IC50 = 15.4 ± 1.56 µM), 11 (IC50 = 19.6 ± 0.62 µM), 12 (IC50 = 30.7 ± 1.49 µM), 15 (IC50 = 12.0 ± 0.16 µM), 21 (IC50 = 13.7 ± 0.40 µM) and 22 (IC50 = 22.0 ± 0.14 µM) showed promising β-glucuronidase inhibition activity, better than the standard (D-saccharic acid-1,4-lactone, IC50 = 48.4 ± 1.25 µM).

Synthesis of Benzophenonehydrazone Schiff Bases and their In Vitro Antiglycating Activities

Benzophenonehydrazone Schiff bases 1-25 were synthesized and their in vitro antiglycation potential has been studied. Out of twenty-five compounds, thirteen showed varying degrees of antiglycation activity with IC50 values ranging between 25.7 - 305 μM, if compared with the standard rutin (IC50 = 70.5 ± 0.50 μM). Compounds 21 (2,3- dihydroxybenzaldehyde N-(diphenylmethylene)hydrazine) IC50 = 25.7 ± 0.003 μM, 14 (diphenylmethanone N-[1-(2,4- dihydroxy-5-nitrophenyl)ethylidene]hydrazine) IC50 = 36.6 ± 0.004 μM, 6 (3,4-dihydroxybenzaldehyde N- (diphenylmethylene)hydrazine) IC50 = 49.5 ± 0.001 μM, 13 (diphenylmethanone N-[1-(2,5-dihydroxyphenyl)ethylidene] hydrazine) IC50 = 52.6 ± 0.023 μM, and 15 (diphenylmethanone N-[1-(3,4-dihydroxyphenyl)ethylidene]hydrazine) IC50 = 57 ± 0.002 μM, showed showed much better antiglycation potential superior to the standard rutin. The compounds 7 (2,5- dihydroxybenzaldehyde N-(diphenylmethylene)hydrazine) IC50 = 66 ± 0.002 μM, and 25 (diphenylmethanone N-[1-(2,5- dihydroxyphenyl)propylidene] hydrazine) IC50 = 67.9 ± 0.001 μM showed compareably good antiglycation activity to standard rutin. All compounds were characterized by spectroscopic techniques and gave satisfactory elemental analysis.

Oxindole Derivatives: Synthesis and Antiglycation Activity

Oxindole derivatives 3-25 have been synthesized from commercially available oxindole by refluxing with different aromatic aldehydes in good yields. Their in vitro antiglycation potential has been evaluated. They showed a varying degree of antiglycation activity with IC50 values ranging between 150.4 - 856.7 µM. 3-[(3-Chlorophenyl)methylidene]- 1,3-dihydro-2H-indol-2-one (IC50 = 150.4 ± 2.5 µM) is the most active compound among the series, better than the standard rutin with an IC50 value 294.5 ± 1.50 µM. The structures of the compounds were elucidated by 1H-NMR and mass spectroscopy and elemental analysis. A limited structure-activity relationship has been developed.

6-Nitrobenzimidazole derivatives: Potential phosphodiesterase inhibitors: Synthesis and structure-activity relationship

6-Nitrobenzimidazole derivatives (1-30) synthesized and their phosphodiesterase inhibitory activities determined. Out of thirty tested compounds, ten showed a varying degrees of phosphodiesterase inhibition with IC(50) values between 1.5±0.043 and 294.0±16.7 μM. Compounds 30 (IC(50)=1.5±0.043 μM), 1 (IC(50)=2.4±0.049 μM), 11 (IC(50)=5.7±0.113 μM), 13 (IC(50)=6.4±0.148 μM), 14 (IC(50)=10.5±0.51 μM), 9 (IC(50)=11.49±0.08 μM), 3 (IC(50)=63.1±1.48 μM), 10 (IC(50)=120.0±4.47 μM), and 6 (IC(50)=153.2±5.6 μM) showed excellent phosphodiesterase inhibitory activity, much superior to the standard EDTA (IC(50)=274±0.007 μM), and thus are potential molecules for the development of a new class of phosphodiesterase inhibitors. A structure-activity relationship is evaluated. All compounds are characterized by spectroscopic parameters.

Evaluation of the thiazole Schiff bases as \(\upbeta \)-glucuronidase inhibitors and their in silico studies

Twenty eight (28) derivatives 2–29 were synthesized and four analogs were found to exhibit single-digit