Analogue 1b Research Articles

Synthesis and Pharmacological Evaluation of Selective Histone Deacetylase 6 Inhibitors in Melanoma Models.

Only a handful of therapies offer significant improvement in the overall survival in cases of melanoma, a cancer whose incidence has continued to rise in the past 30 years. In our effort to identify potent and isoform-selective histone deacetylase (HDAC) inhibitors as a therapeutic approach to melanoma, a series of new HDAC6 inhibitors based on the nexturastat A scaffold were prepared. The new analogues 4d, 4e, and 7b bearing added hydrophilic substituents, so as to establish additional hydrogen bonding on the rim of the HDAC6 catalytic pocket, exhibit improved potency against HDAC6 and retain selectivity over HDAC1. Compound 4d exhibits antiproliferative effects on several types of melanoma and lymphoma cells. Further studies indicates that 4d selectively increases acetylated tubulin levels in vitro and elicits an immune response through down-regulating cytokine IL-10. A preliminary in vivo efficacy study indicates that 4d possesses improved capability to inhibit melanoma tumor growth and that this effect is based on the regulation of inflammatory and immune responses.

Iron-Strapped Porphyrins with Carboxylic Acid Groups Hanging over the Coordination Site: Synthesis, X-ray Characterization, and Dioxygen Binding.

A series of myoglobin active site analogues were synthesized and characterized to investigate the dioxygen binding effects of a flexible distal strap over the coordination site. These four synthetic models differ mostly by the shape and polarity of their cavities and also possibly by motion of the distal strap attached to two of the meso carbon atoms. Each of the four models has an intramolecular nitrogen base that axially binds the iron(II) cation inside the porphyrin, but they differ either by the nature of the distal strap or by its mobility. The overhanging distal group is either a generally apolar ethyl malonate group or a polar malonic acid group which is also a strong H-bond donor. It is shown that, in the ferrous complex 2b bearing such an overhung malonic acid group in close proximity to the iron atom, the equilibrium rate for dioxygen binding is significantly enhanced in comparison to that of its ester precursor. In the case of the analogous complex 1b bearing a more mobile distal strap, one of the carboxylic acid groups binds the iron(II) cation, leading to a six-coordinate ferrous complex. Unexpectedly, this complex proved to be high-spin (S = 2) as shown by solid-state magnetic measurements. Whereas this unprecedented complex still binds dioxygen, the formation of the intramolecular six-coordinate complex precluded the measurement of its dioxygen affinity through direct quantitative gas titration monitored by UV-vis spectroscopy. However, in this case, the determination of the kinetic rate constants for dioxygen binding and dissociation by laser flash photolysis allowed the evaluation of the equilibrium rate. Together with three previous X-ray structures of iron complexes in the ααββ conformation, the structure of the cavity and the shape of the relaxed distal strap are also discussed with the consideration of the resolution of X-ray structures of two different free-base ligands in the ααββ conformation, with one bearing the ethyl malonate group and the second one bearing the malonic acid group. A third X-ray structure of the analogous ligand with the overhanging ethyl malonate group in the αβαβ series allows a direct comparison of the distal strap in both geometries. This work reveals that the compound with the overhanging carboxylic acid group which cannot directly interact with the ferrous heme exhibits an increased dioxygen affinity by 2 orders of magnitude versus its ester precursor.

Investigating the Antibacterial Activity of Biphenylthiazoles against Methicillin- and Vancomycin-Resistant Staphylococcus aureus (MRSA and VRSA).

Phenylthiazoles were reported previously as a new scaffold with antibacterial activity against an array of multidrug-resistant staphylococci. However, their promising antibacterial activity was hampered in large part by their short half-life due to excessive hepatic clearance. Close inspection of the structure-activity-relationships (SARs) of the phenylthiazoles revealed two important structural features necessary for antibacterial activity (a nitrogenous and a lipophilic component). Incorporating the nitrogenous part within a pyrimidine ring resulted in analogues with a prolonged half-life, while the biphenyl moiety revealed the most potent analogue 1b. In this study, advantageous moieties have been combined to generate a new hybrid scaffold of 5-pyrimidinylbiphenylthiazole with the objective of enhancing both anti-MRSA activity and drug-like properties. Among the 37 tested biphenylthiazoles, piperazinyl-containing derivatives 10, 30, and 36 were the most potent analogues with MIC values as low as 0.39 μg/mL. Additionally, 36 exhibited significant improvement in stability to hepatic metabolism.

Pyrano[2,3,4-cd]indole as a Scaffold for Selective Nonbasic 5-HT6R Ligands.

In this letter, we report the synthesis of a pyrano[2,3,4-cd]indole chemical scaffold designed through a tandem bioisostere generation/virtual screening protocol in search of 5-HT6R ligands. The discovered chemical scaffold resulted in the design of highly active basic and nonbasic 5-HT6R ligands (5-HT6R Ki = 1 nM for basic compound 6b and 5-HT6R Ki = 4 nM for its neutral analog 7b). Additionally, molecular modeling suggested that the hydroxyl group of nonbasic ligands 7a-7d forms hydrogen bonds with aspartic acid D3×32 or D7.36×35.

Synthesis, structure, photophysical and electrochemical properties of Ru(TFA)(CO)(PPh3)2(L) (L=2-phenylpyridine, 2-p-tolylpyridine) and Ru(CO)(PPhMe2)2(L)(L′) (L= TFA, H) (L′= bipyridine, L′= 4,4′-dimethylbipyridine) relationships between ancillary ligand structure and luminescent properties

The synthesis, structure and photophysical properties of the complexes [Ru[(CO)(TFA) (PPh3)2(L)][(L = ppy = 2-phenylpyridine, (1a); L = 2–(p–tolyl)pyridine] (1b), are reported. The complexes were characterized by UV-VIS, IR and NMR and by single-crystal X-ray diffraction techniques. We also report the synthesis, structure and photophysical properties of [Ru(CO)(L)(PPhMe2)2(L′)]+[PF6]− [L′ = bipyridine, L = TFA, (3a); L = H, (3b) and L = H, L′ = 4,4′-dimethlyl bipyridine (3c)]. These compounds were characterized by UV-VIS, IR and NMR techniques and by a single crystal X-ray diffraction in the case of 3a. The solid state structure of [Ru(Me2PhP)2(CO)2(TFA)2(2) which is the starting material for the synthesis 3a-3c is also reported to verify the trans relationship of the less bulky PPhMe2 and for comparison with the previously reported PPh3 analogs. The purpose of this study was to determine the impact, if any, of replacing bpy with ppy in the case of 1a and alkylation of the benzene ring in the case of 1b on the photophysical and electrochemical properties compared to related Ru(bpy) complexes. In contrast to the bpy analogs 1a and 1b showed reversible 1e− oxidations and blue-shifted MLCT absorptions. In the case of 3a-3c we were interested in the effect on the photophysical properties of substituting PPh3 with the less bulky but more electron donating PPhMe2. There were only minor changes in the photophysical and electrochemical properties relative to the previously reported PPh3 analogs.

Facile synthesis of new divergent imidazole-containing ligands for a 1-D cobalt(II) coordination polymer

A new divergent ligand (3a) containing a triaryl core and two imidazole side-arms has been designed and synthesized. The synthetic procedure utilizes a two-step strategy, i.e. the Kröhnke condensation, followed by a Cu-catalyzed Ullman-type coupling. This synthetic strategy allows the facile introduction of various substituents on the 4-position of the central pyridine in the ligands, which was proved by the synthesis of a ligand analog (3b). The new ligands were well characterized by spectroscopic methods and X-ray structural analysis was carried out for 3a. Reaction of 3a with Co(NCS)2 by a layering method afforded single crystals of a coordination polymer 5, which was structurally characterized by X-ray diffraction. 5 is composed of two ligands and one Co(NCS)2 in its asymmetric unit and features a 1-D coordination polymer with nano-scale metallomacrocyles. The structure of 5 is found to be quite different from all known coordination networks composed of Co(NCS)2 and closely related divergent ligands.

Synthesis, in vitro Antiproliferative and Antiinflammatory Activities, and Kinase Inhibitory effects of New 1,3,4-triarylpyrazole Derivatives

Pyrazole derivatives have been reported as both anticancer and antiinflammatory agents. This study was conducted to develop new pyrazole derivatives as potential anticancer and/or antiinflammatory agents. Their molecular mechanisms of action have been investigated. a series of new triarylpyrazole derivatives were synthesized. Their in vitro anticancer activity was tested against NCI-58 cancer cell line panel of nine cancer types. The most active compound 1a was tested against sixteen kinases, many of them are known to be over-expressed in leukemia and breast cancer. The most sensitive kinases were V600E-B-RAF, C-RAF, FLT3, and P38α/MAPK14. Compound 1a was further tested for caspase-3/7 activity and LDH release assay as measures of its apoptotic and necrotic activities against RPMI-8226. Moreover, the ability of compounds 1a, 1b, and 1g to inhibit nitric oxide and prostaglandin Eproduction in LPS-induced RAW 264.7 macrophages was also examined. Compounds 1a, 1c, and 1g showed the highest activities against the cancer cell line panel, with more inhibitory effects against leukemia and breast cancer subpanels. The highest activity was exerted by compound 1a. Its IC50 values against RPMI-8226, K-562 leukemia cell lines, and MDA-MB-468 breast cancer cell line were 1.71 μM, 3.42 μM, and 6.70 μM, respectively. The IC50 of compound 1a against P38α/MAPK14 kinase was 0.515 μM. The caspase activity was increased by 72% and 170% at 1.23 μM and 3.70 μM concentrations of compound 1a, respectively. Furthermore, compound 1b inhibited 80.26% and 95.31% of NO and PGE2 productions, respectively, at 50 μM concentration in the LPS-induced RAW 264.7 macrophages. Compound 1a could kill the cells through induction of apoptosis rather than necrosis. Compound 1a was more selective against cancer cells than non-cancerous cells. In addition, the hydroxyl analogue 1b was the most active as antiinflammatory agent.

Design, synthesis and anticancer properties of IsoCombretaQuinolines as potent tubulin assembly inhibitors

The synthesis and evaluation of a new series of IsoCombretaQuinolines (IsoCoQuines) 2 with a 2-substituted-quinoline in place of the 3,4,5-trimethoxyphenyl ring present in isoCA-4 and CA-4 are described. Most of these compounds displayed a potent cytotoxic activity (IC50 < 10 nM) against a panel of five human cancer cell lines and inhibited tubulin assembly at a micromolar level. The most potent analogue 2b, having a 3-hydroxy-4-methoxyphenyl as B-ring, led to cell cycle arrest in G2/M phase. Docking studies indicate that 2b showed a binding mode comparable to those previously observed with quinazoline analogous (IsoCoQ) and with isoCA-4 at the colchicine binding site of tubulin.

Synthesis, DNA binding and antitrypanosomal activity of benzimidazole analogues of DAPI

A series of novel benzimidazole diamidines were prepared from the corresponding dicyano analogues either by applying Pinner methodology (5a–c, 10 and 13a) or by making amidoximes intermediates that were reduced to the corresponding amidines (15a–c). The new amidines were evaluated in vitro against the protozoan parasite Trypanosoma brucei rhodesiense (T. b. r.). The thiophene analogue 5b and the N-methyl compound 15a showed superior antitrypanosomal activity compared to that of the parent I.

Regiodiscriminating Reactivity of Isolable NHC-Coordinated Disilenyl Germylene and Its Cyclic Isomer.

An isolable NHC-coordinated disilenyl germylene R2Si═SiR-GePh·NHCiPr2Me2 (5b: R = 2,4,6-triisopropylphenyl, NHCiPr2Me2 = 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene) is obtained from the reaction of the α-chloro silyl functionalized heavier vinylidene analogue R2(Cl)Si-RSi═Ge·NHCiPr2Me2 with phenyllithium. The disilenyl germylene 5b isomerizes at 40 °C to the NHC-adduct of the corresponding heavier cyclopropylidene analogue 6b. Both 5b and 6b display near perfect regiodiscrimination in their reactions with phenylacetylene and xylyl isocyanide, affording in the case of each reagent two different regioisomers of NHC-coordinated cyclic germylenes. DFT calculations reveal that the Si═Si bond accounts for the high reactivity of 5b even at low temperature while in the case of cyclic 6b the low-valent germanium center requires a considerable thermal activation.

Synthesis, in Vitro Evaluation, and Radiolabeling of Fluorinated Puromycin Analogues: Potential Candidates for PET Imaging of Protein Synthesis.

There is currently no ideal radiotracer for imaging of protein synthesis rate (PSR) by positron emission tomography (PET). Existing fluorine-18-labeled amino acid-based radiotracers predominantly visualize amino acid transporter processes, and in many cases they are not incorporated into nascent proteins at all. Others are radiolabeled with the short-half-life positron emitter carbon-11, which is rather impractical for many PET centers. Based on the puromycin (6) structural manifold, a series of 10 novel derivatives of 6 was prepared via Williamson ether synthesis from a common intermediate. A bioluminescence assay was employed to study their inhibitory action on protein synthesis, which identified the fluoroethyl analogue 7b as a lead compound. The fluorine-18 analogue was prepared via nucleophilic substitution of the corresponding tosylate precursor in a modest radiochemical yield of 2 ± 0.6% with excellent radiochemical purity (>99%) and showed complete stability over 3 h at ambient temperature.

Effect on catecholase activity and interaction with biomolecules of metal complexes containing differently tuned 5-substituted ancillary tetrazolato ligands

Four new metal complexes (one mononuclear and three dinuclear) viz. [NiL(5-phenyltetrazolato)] (1a), [Ni2L2{5-(2-cyanophenyl)-tetrazolato}2] (1b), [Cu2L2{5-phenyltetrazolato}2]·C6H5CN (2a) and [Cu2L2{5-(2-cyanophenyl)-tetrazolato}2] (2b) [HL=3-(2-dimethylamino-ethylimino)-1-phenyl-butan-1-one] have been synthesized by in-situ generation of tetrazolato ligands and characterized by X-ray crystallography, different spectroscopic techniques and elemental analyses. Introduction of one nitrile group in the 5-substituted phenyl ring makes the tetrazolato ligand comparatively weaker donor leading the complex to be more vulnerable towards dissociation facilitating subsequent substrate binding for catecholase oxidation study. Copper complex 2b has been found to be more active with respect to analogous nickel complex 1b as it provides the metal centered oxidation route rather than ligand centered oxidation in nickel complex. The comparative catalytic activities of complex 1b and 2b are further explored by DFT calculations which also support the experimental results. UV–Vis and fluorescence-based spectroscopic techniques revealed that two of the metal-tetrazolato complexes (1a and 2b) interact with double stranded DNA via intercalation and also with serum albumin protein BSA. A comparative assessment indicated that the Ni(II)-tetrazolato complex 1a displayed superior DNA binding. The interaction of these compounds with bovine serum albumin (BSA) suggested that the Cu(II)-tetrazolato complex 2b quenched the intrinsic fluorescence of BSA in a static quenching process and shows stronger binding constant.

Design, Synthesis, and Cytotoxicity Evaluation of 3‐(5‐(3‐(aryl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐1‐phenyl‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)pyridine and 5‐(3‐(aryl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐3‐(pyridin‐3‐yl)‐4,5‐dihydropyrazole‐1‐carbaldehyde Derivatives as Potential Anticancer Agents

In an attempt to find bio‐active small molecules, a series of novel 3‐(5‐(3‐(aryl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐1‐phenyl‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)pyridine 5a–i and 5‐(3‐(aryl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐3‐(pyridin‐3‐yl)‐4,5‐dihydropyrazole‐1‐carbaldehyde 6a–i were designed, synthesized, and evaluated for their in vitro cytotoxic activity against a panel of human cancer cell lines namely; HeLa (human cervix), NCI‐H460 (human lung), PC‐3 (human prostate), and NIH‐3T3 (mouse embryo fibroblasts) normal cell line. Most of these compounds exhibited moderate to good cytotoxic activity against the tested cancer cell lines and weak toxicity against normal cell line. Analogues 5b, 5f, 5g, 6b, and 6g showed significant cytotoxicity as compared to standard drug etoposide. Among all the synthesized compounds, compound 6g displayed superior cytotoxicity with an IC50 value of 7.98 ± 1.08 μM for Hela cancer cell line.

An efficient method for synthesis of bexagliflozin and its carbon-13 labeled analogue

A convenient method for highly diastereoselective synthesis of bexagliflozin 7a and its carbon-13 labeled analogue 7b was developed. The main feature is the stereoselective reduction of 16 catalyzed by BF3·OEt2. Furthermore, the cocrystallization skill was firstly used for the purification of bexagliflozin and its analogue. The carbon-13 labeled bexagliflozin 7b was firstly prepared in five steps and in 57% overall chemical yield starting from the commercially available d-gluconolactone-[13C6].

Polyprenylated Tetraoxygenated Xanthones from the Roots of Hypericum monogynum and Their Neuroprotective Activities.

Ten new polyprenylated tetraoxygenated xanthones, monogxanthones A-J (1-10), together with eight known analogues (4b, 11-17) were identified from the roots of Hypericum monogynum. The structures of these new polyprenylated xanthones (1-10), a class of compounds rarely found in plants of the genus Hypericum, were elucidated by the interpretation of their HRESIMS, 1D and 2D NMR, and electronic circular dichroism data. Compounds 1 and 2 exhibited neuroprotective effects against corticosterone (Cort)-induced lesions of PC12 cells at concentrations of 6.25, 12.50, and 25.00 μM, with cell viability greater than 75%, as well as inhibitory effects on nitric oxide production in lipopolysaccharide-induced BV2 microglia cells, with IC50 values of 7.47 ± 0.65 and 9.60 ± 0.12 μM, respectively. Collectively, these results shed new light on the potential of polyprenylated xanthones from the genus Hypericum in the development of antidepression therapies.

Synthesis, structures elucidation, DNA-PK, PI3K and antiplatelet activity of a series of novel 7- or 8-(N-substituted)-2-morpholino-quinazolines

The DNA-dependent protein kinase and phosphoinositide 3-kinase family is one of the most frequently activated enzymes in a wide range of human cancers; consequently, inhibition of DNA-dependent protein kinase and phosphoinositide 3-kinase represents an approach for cancer therapy. In this work, we have designed and synthesized a series of novel 7- or 8-(N-substituted)-2-morpholino quinazolines 3a–f, 5a–e, 7a–e, and 9 from 7- or 8-amino-2-morpholino quinazolin-4-ones (2a, 4a), the 3-methyl analogues (2b, 4b) and the 4-alkyloxy analogues (6a–b, 8). The compounds were subsequently assayed for DNA-dependent protein kinase and phosphoinositide 3-kinase activity. Most compounds were less active than expected in spite of the strong structural resemblance to the previously studied 7- or 8-(O-substituted)-2-morpholino-1,3-benzoxazine inhibitors. Loss of DNA-dependent protein kinase activity for the quinazolin-4-ones (3a–d and 5a–d) has been attributed to tautomerization to the aromatic enol (4-OH) tautomers. Aromatization of the heterocyclic ring could alter the conformation, and thus binding position, resulting in reduced compound-receptor hydrogen bonding of the morpholine oxygen and 4-carbonyl oxygen. The hetero-aromatic compounds 7a–e and 9 also did not show any DNA-dependent protein kinase activity at 10 µM, which supports the above hypothesis. Compound 7c (R=CH2(pyridine-4-yl)) displayed selective phosphoinositide 3-kinase delta activity with 80 % inhibition at 10 µM. Similarly, compounds 5a (8-N-substituted, R=CH2Ph) and 3a (7-N-substituted, R=CH2Ph) showed selective phosphoinositide 3-kinase beta activity with 69 and 61 % inhibition, respectively. Antiplatelet inhibition assays showed that compound 7e with the 4-O-benzyloxy group and 8-CH2(pyridine-3-yl) substituents was found to be the most active (IC50 35 µM).

Organic dyes containing fluorenylidene functionalized phenothiazine donors as sensitizers for dye sensitized solar cells

Two new organic sensitizers featuring fluorenylidene decoration on the phenothiazine donor have been synthesized and characterized as sensitizers for nanocrystalline TiO2-based dye sensitized solar cells (DSSCs). The dyes possess cyanoacrylic acid as acceptor/anchoring group and a conjugation pathway composed of fluorene and thiophene. Introduction of the fluorenylidene moiety on phenothiazine enhances the optical density of the dyes while the extension of conjugation by thiophene insertion red-shifts the absorption peak originating from the intramolecular charge transfer from phenothiazine to cyanoacrylic acid. The ground and excited state oxidation potentials of the fluorenylidene-containing dyes are upwardly shifted when compared to the parent dyes indicating a π-delocalized donor segment. The electronic properties were supported by density functional theoretical computations. Among the DSSCs fabricated, the dye (5a) having fluorene and thiophene in the spacer resulted higher power conversion efficiency (3.31 %) than the corresponding bithiophene analog (5b, 2.83 %) attributable to the relatively high electron life time and enhanced resistance for recombination in the former.

Novel Piperine Derivatives with Antidiabetic Effect as PPAR-γ Agonists.

Piperine is an alkaloid responsible for the pungency of black pepper. In this study, piperine isolated from Piper nigrum L. was hydrolyzed under basic condition to obtain piperic acid and was used as precursor to carry out the synthesis of twenty piperine derivatives containing benzothiazole moiety. All the benzothiazole derivatives were evaluated for their antidiabetic potential by OGT test followed by assessment of active derivatives on STZ-induced diabetic model. It was observed that nine of twenty novel piperine analogues (5b, 6a-h), showed significantly higher antidiabetic activity in comparison with rosiglitazone (standard). Furthermore, these active derivatives were evaluated for their action as PPAR-γ agonists demonstrating their mechanism of action. The effects on body weight, lipid peroxidation, and hepatotoxicity after administration with active derivatives were also studied to further establish these derivatives as lead molecules for treatment of diabetes with lesser side-effects.

Design, synthesis, broad-spectrum antiproliferative activity, and kinase inhibitory effect of triarylpyrazole derivatives possessing arylamides or arylureas moieties

A novel series of 1,3,4-triarylpyrazole derivatives possessing terminal arylamide or arylurea terminal moieties has been designed and synthesized. Their in vitro antiproliferative activities were investigated against a panel of 58 cell lines of nine different cancer types at the NCI, USA. The urea analogues 2b, 2c, and 2f as well as the amide derivatives 3e and 3f exerted the highest mean % inhibition values over the 58 cell line panel at 10 μM, and thus were further tested in 5-dose testing mode to determine their GI50, TGI, and LC50 values. The above mentioned compounds have shown stronger antiproliferative activities in terms of potency and efficacy upon comparing their results with Sorafenib as a reference compound. Among them, compounds 2c and 2f possessing 3,4-dichlorophenylurea terminal moiety showed the highest mean %inhibition value of about 99.85 and 104.15% respectively over the 58-cell line panel at 10 μM concentration. Also compounds 2b, 3e, and 3f exhibited mean % inhibition over 80% at 10 μM concentration. The GI50 value of compound 3e over K-562 cancer cell line was 0.75 μM. Accordingly, compound 2f was screened over seven kinases at a single-dose concentration of 10 μM to profile its kinase inhibitory activity. Interestingly, the compound showed highly inhibitory activities (90.44% and 87.71%) against BRAF (V600E) and RAF1 kinases, respectively. Its IC50 value against BRAF (V600E) was 0.77 μM. Compounds 2b, 2c, 2f, 3e, and 3f exerted high selectivity towards cancer cell lines than L132 normal lung cells.

Design, synthesis and evaluation of specific TNF-alpha inhibitory novel dithioic acid derivatives from natural acids as anti inflammatory agents

Novel dithioic acid derivatives have been synthesized from 3 different natural acids having marked anti-inflammatory activities including ferulic acid, cinnamic acid and salicylic acid. The structures of the new compounds were established on the basis of IR, 1H NMR and mass spectral data. In silico molecular analysis of different dithioic acid analogues of natural acids were done, and the compounds which obeyed Lipinski's rule of five were taken for computing molecular descriptors. Docking studies were carried out against target, human TNF-? converting enzyme (TACE). Out of the seventeen analogues docked, compound 1b, 2b and 3b exhibited minimum glide score and were taken out for wet laboratory synthesis and validations. Compound 1b ({5-[(E)-2-(4-hydroxy-3-methoxyphenyl) ethenyl]-1, 3, 4-thiadiazol-2-yl}carbamodithioic acid) was screened for in vitro anti-TNF-? study, and compounds 1b, 2b and 3b for in vivo anti-inflammatory activity. In vitro specific TNF-? inhibitory activity of the ferulic acid analogue (1b) was evaluated using Reverse transcriptase- polymerized chain reaction. In vitro and in vivo anti-inflammatory activity was also evaluated using the HRBC membrane stabilization method and carrageenan induced rat paw edema method and compared with standard drug (diclofenac sodium). Among all derivatives 1b (ferulic acid derivative) showed maximum percentage inhibition (60.09%) while the remaining compounds showed moderate inhibition.