Antioxidant, anti-inflammatory, and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives.

The synthesized flavonoid derivatives were examined for their antioxidant, anti-inflammatory, xanthine oxidase (XO), urease inhibitory activity, and cytotoxicity. Except few, all the flavonoids under this study showed significant antioxidant activity (45.6%-85.5%, 32.6%-70.6%, and 24.9%-65.5% inhibition by DPPH, ferric reducing/antioxidant power, and oxygen radical absorption capacity assays) with promising TNF-α inhibitory activity (42%-73% at 10 µM) and IL-6 inhibitory activity (54%-81% at 10 µM) compared with that of control dexamethasone. The flavonoids luteolin, apigenin, diosmetin, chrysin, O3Ꞌ , O7 -dihexyl diosmetin, O4Ꞌ , O7 -dihexyl apigenin, and O7 -hexyl chrysin, showed an inhibition with IC50 values (4.5-8.1 µg/mL), more than allopurinol (8.5 µg/mL) at 5 µM against XO and showing more than 50% inhibition at a final concentration (5 mM) with an IC50 value of ranging from 4.8 to 7.2 (µg/mL) in comparison with the positive control thiourea (5.8 µg/mL) for urease inhibition. Thus, the flavonoid derivatives may be considered as potential antioxidant and antigout agents.

Synthesis and biological evaluation of asymmetric indole curcumin analogs as potential anti-inflammatory and antioxidant agents.

Abstract A series of asymmetric indole curcumin analogs were synthesized and evaluated as possible inhibiters of pro-inflammatory enzymes such as COX-2, pro-inflammatory cytokines as TNF-α and IL-6, trypsin and ß-glucuronidase. They were also tested for antioxidant activities. The results showed that compounds 5e and 5h were found to be the most potent inhibitors of COX-2 (83.33%, 82.50%) and ß-glucuronidase (67.80%, 64.12%). All the synthesized compounds exhibited promising activity against IL-6 in a range of 71-100% at 10 µM concentration. Compounds 5f, 5h, 5e, 5c and 5d showed significant inhibition against TNF-α (28-51%) and IL-6 (87-98%) with low toxicity (45-51%) against CCK-8 cells. With few exceptions, all other compounds were found to be good to excellent inhibitors of IL-6 and moderate inhibitors of TNF-α; however, the toxicity profiles of these compounds need to be ameliorated in further optimization studies. Amongst the tested compounds, 5c, 5b, 5j and 5g were found to possess excellent reducing activity and 5b, 5c and 5h were moderate DPPH (1,1-diphenyl-2-picryl hydrazine) radical scavengers.

Synthesis of novel carbazole chalcones as radical scavenger, antimicrobial and cancer chemopreventive agents.

A series of novel carbazole chalcones has been synthesised and evaluated for radical scavenging activity, cytotoxicity and antimicrobial activities. Compounds 12m, 12o and 12c exhibited good 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, compounds 12e, 12m and 12d were excellent hydroxyl radical scavengers and compounds 12a, 12e, 12g, 12n and 12m have shown inhibition of oxidative DNA damage induced by 2,2'-azobis (2-amidinopropane hydrochloride). Compounds 12j, 12i, 12n, 12c, 12m and 12e were most active against the selected cancer cell lines. Compounds 12a, 12e and 12m showed good antibacterial activity and compounds 12h and 12m have shown good antifungal activity. All the compounds were subjected for absorption, distribution, metabolism and excretion (ADME) predictions by computational method and found that these molecules could be considered as potential candidates for oral drug development.

Synthesis and biological evaluation of novel series of aminopyrimidine derivatives as urease inhibitors and antimicrobial agents.

A novel series of carbazole substituted aminopyrimidines (5a-p) were synthesized and screened for their in vitro urease inhibition and antimicrobial activity. Among the compounds, 4-(2,4-dichlorophenyl)-6-(9-methyl-9H-carbazol-3-yl)-pyrimidin-2-amine (5i) was found to be the most potent showing urease inhibitory activity with an IC50 value 19.4 ± 0.43 µM. Compounds 5c, 5g, 5j and 5o showed good activity against all selected bacterial strains and compounds 5b, 5c, 5m and 5o showed good activity against selected fungal strains. All the compounds were subjected for ADME predictions by computational method.

Synthesis, biological evaluation, and docking studies of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines as potent anti-inflammatory and antioxidant agents.

A novel series of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines (5a-o) has been synthesized and the structures of newly synthesized compounds were characterized by IR, (1)H NMR and mass spectral analysis. All the synthesized compounds were evaluated for their in vitro and in vivo anti-inflammatory activity, and also for their antioxidant activity. Compounds 5b, 5c, 5d and 5n were found to be selective COX-2 inhibitors. Compound 5c was found to potent inhibitor of the carrageenin induced paw edema in rats. Most of the compounds exhibited good DPPH and superoxide radical scavenging activity, while compounds 5c, 5d, 5i and 5k exhibited good hydroxyl radical scavenging activity. Molecular docking result, along with the biological assay data, suggested that compound 5c was a potential anti-inflammatory agent.

Synthesis, biological evaluation, and molecular docking of N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives as xanthine oxidase and tyrosinase inhibitors.

Claisen-Schmidt condensation of 3-formyl-9-methylcarbazole with various amides of 3-aminoacetophenone afforded N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives. All compounds were investigated for their in vitro xanthine oxidase (XO), tyrosinase and melanin production inhibitory activity. Most of the target compounds had more potent XO inhibitory activity than the standard drug (IC(50) = 4.3-5.6 µM). Interestingly, compound 7q bearing cyclopropyl ring was found to be the most potent inhibitor of XO (IC(50) = 4.3 µM). Molecular modelling study gave an insight into its binding modes with XO. Compounds 7a, 7d, 7e, 7g, and 7k were found to be potent inhibitors of tyrosinase (IC(50) = 14.01-17.52 µM). These results suggest the possible use of these compounds for the design and development of novel XO and tyrosinase inhibitors.

Synthesis and antioxidant, cytotoxicity and antimicrobial activities of novel curcumin mimics.

Claisen-Schmidt condensation of 3-(1,2,3,6-tetrahydro-1-methylpyridin-4-yl)-2,4,5- trimethoxybenzaldehyde 3 and various aromatic, heterocyclic and alicyclic amides of 3- aminoacetophenone 6(a-s) afforded novel curcumin mimics. All the synthesized compounds were characterized by IR, (1)H NMR, Mass spectroscopy and evaluated for antioxidant, cytotoxicity and antimicrobial activity. Out of the 20 compounds screened, compounds 7i, 7l, 7q, and 7n have shown excellent radical scavenging activity, compounds 7o, 7t, 7f, and 7r have shown significant xanthine oxidase inhibition, and compounds 7a, 7k and 7l were found to be potent inhibitors of selected cancer cell lines. Compounds 7h, 7t, 7l, 7i, and 7e have shown good antibacterial activity, whereas compounds 7j, 7f, 7o, 7h, and 7t exhibited significant antifungal activity.

Synthesis and biological evaluation of nitrogen-containing benzophenone analogues as TNF-alpha and IL-6 inhibitors with antioxidant activity.

A series of nitrogen-containing benzophenone analogues were synthesized by Mannich reaction and evaluated for the inhibition of pro-inflammatory cytokines, TNF-alpha and IL-6. DPPH (1,1-diphenyl-2-picryl hydrazine) radical scavenging activity and its kinetics were studied to determine the antioxidant potential of the test samples. All the synthesized compounds exhibited promising activity against IL-6 in a range of 81-89%, 09-42% at 10 and 1 microM, respectively, concentration. Exceptionally, the compound 20e was observed to be an effective inhibitor of TNF-alpha (54%) and IL-6 (97%), (47%) at 10 and 1 microM concentrations with minimum toxicity (22%) against CCK-8 cells. With few exceptions, all other compounds were found to be excellent inhibitors of IL-6 and moderate to excellent inhibitors of TNF-alpha, however the toxicity profiles of these compounds need to be ameliorated in further optimization studies. Amongst the tested compounds, 16a, 17g, 18f, 18g, 19g and 20e were found to possess significant antioxidant activity.

Synthesis and biological evaluation of nitrogen-containing chalcones as possible anti-inflammatory and antioxidant agents.

A novel series of nitrogen-containing chalcones were synthesized by Mannich reaction and were screened for anti-inflammatory related activities such as inhibition of cyclooxygenase-2 (COX-2), trypsin and beta-glucuronidase. The antioxidant potential was demonstrated using 1,1-diphenyl-2-picryl hydrazine (DPPH) radical scavenging activity. The results of the above studies shows that the compounds synthesized were found to be effective inhibitors of above pro-inflammatory enzymes, and were found to be possess moderate radical scavenging potential. Overall, the results of the studies reveal that the chalcones with N-methyl piperazine methyl and piperidine methyl substitution (4c, 3b, 4d, 6b) seems to be important for inhibition of beta-glucuronidase. Whereas the chalcones with piperidine methyl substitution (8b, 7b, 7c, 6c, 4b, 3c, 3b) were observed as effective inhibitors of COX-2, while the same compounds were found to be less reactive against COX-1 as compared to COX-2.