C. V. Kavitha

Synthesis and pharmacological evaluation of novel N-alkyl/aryl substituted thiazolidinone arecoline analogues as muscarinic receptor 1 agonist in Alzheimer's dementia models

Earlier we have reported the effect of arecoline thiazolidinone and morpholino arecoline analogues as muscarinic receptor 1 agonist in Alzheimers dementia models. To elucidate further our SAR study on the chemistry and muscarinic receptor binding efficacy, a series of novel N-alkyl/aryl substituted thiazolidinone arecoline analogues 6(a-m) were designed and synthesized from 3-pyridine carboxaldehyde by reacting with different amines in the presence of gamma-ferrite as catalyst and subjected to in vitro muscarinic receptor binding studies using male Wistar rat brain membrane homogenate and extended to in vivo pharmacological evaluation of memory and learning in male Wistar rats. Derivative 6j having diphenylamine moiety attached to nitrogen of thiazolidinone showed significant affinity for the M1 receptor binding.

A small oxazine compound as an anti-tumor agent: a novel pyranoside mimetic that binds to VEGF, HB-EGF, and TNF-α.

A novel pyranoside mimetic compound, DMBO (2-(2,6-difluorophenyl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecane), was designed and synthesized. The sugar mimicking behavior of DMBO was addressed by its ability to bind several growth factors/cytokines such as vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), and tumor necrosis factor (TNF)-α as demonstrated by the recently developed surface plasmon resonance assay. DMBO exhibited strong anti-proliferation activity in vitro against tumor cells including a highly metastatic murine osteosarcoma cell line LM8G7 that secretes VEGF as well as two human ovarian cell lines, OVSAHO and SKOV-3, which secrete TNF-α and HB-EGF respectively. Furthermore, DMBO inhibited the metastatic activity to the mouse liver of LM8G7 cells injected from a lateral tail vein, and affected the heparan-degrading activity of LM8G7 cells. Here, we report that DMBO acts as a human heparanase inhibitor in vitro possibly as a substrate mimetic. DMBO also inhibited the migration and invasion of LM8G7 cells and angiogenic events such as endothelial cell proliferation, migration and capillary tube-like formation in vitro. More prominently, the administration of DMBO with heparin resulted in synergistic anti-tumor effects in mouse modelofosteosarcoma. These preclinical data shows the potential anti-cancer effects of DMBO.

Microwave-Assisted Solvent-Free Synthesis of N-alkyl Benzotriazole Derivatives: Antimicrobial Studies

To elucidate further our structural activity relation on the chemistry and antimicrobial activity, a series of novel N-alkylated benzotriazole derivatives bearing pharmaceutically important substituted biphenyl and benzyl halides were synthesized. The synthesized compounds were characterized and tested for in vitro antimicrobial activities by MIC determination against a panel of susceptible and resistant Gram-positive and Gram-negative microorganisms. The synthesis has been carried out using microwave irradiation method with solvent and without solvent. The obtained results showed high yields. Interestingly, compounds 2a and 2b showed a two fold increased antibacterial activity than the standard drug tested and the compounds 2d and 2e showed potent antifungal activity than the standard drug tested.

Synthesis and X-ray crystal structure analysis of 4-(3, 4-dichlorophenyl)-2-(3, 4, 5-trimethoxy-benzylidene)-3, 4-dihydro-naphthalen-1 (2H)-one: Sertraline key intermediate analog

The novel bioactive compound 4-(3,4-dichlorophenyl)-2-(3,4,5-trimethoxy-benzylidene)-3,4-dihydro-naphthalen-1(2H)-one was synthesised in three different methods, namely, conventional, MW irradiation with solvent and MW irradiation without solvent. The synthesised compound was characterised by spectroscopic techniques and finally confirmed by X-ray crystal structure analysis.

Synthesis and Crystal Structure of 1-(Cyano(4-methoxyphenyl)methyl)cyclohexyl Acetate

The title compound, C17H21NO3, was synthesized by the acetylation of the hydroxy group of 1-(cyano(4-methoxyphenyl)methyl)cyclohexanol, which was formed by the reaction of 4-methoxyphenyl acetonitrile with cyclohexanone. The compound was characterized spectroscopically, and the structure was investigated by X-ray crystallography. The compound crystallizes in the orthorhombic crystal class in the space group Pbca with cell parameters a = 13.412(6) Å, b = 12.398(14) Å, c = 19.026(19) Å and V = 3164(5) Å 3 for Z = 8. The cyclohexane ring is in a chair conformation. The structure exhibits intermolecular hydrogen bonds of the type C–H…N and C–H…O.

Crystal and Molecular Structure of 3-(2-(1-Hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl)-2-(4-p-methylphenyl )-1,3-thiazolidin-4-one

The compound 3-(2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl)-2-(4-methylphenyl)-thiazolidin-4-one was synthesized. The compound crystallizes in the orthorhombic system with space group Pbca and cell parameters are a = 11.795(1) Å, b = 11.727(1) Å, c = 33.964(9) Å, Z = 8, V = 4697.9(2) Å3. The final residual factor is R1 = 0.0647. The molecule exhibits intermolecular hydrogen bond of type O-H···O.

Effect of novel N-arylurea- substituted 3-morpholino arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer’s dementia models

A series of novel, potent, and selective muscarinic receptor 1 agonists (M1 receptor agonists) that employ a key N-substituted morpholine Arecoline moiety has been synthesized as part of research effort for the therapy of Alzheimers diseases. The ester group of arecoline (which is reported as muscarinic agonist) has been replaced by N-substituted morpholine ring. The structure activity relationship reveals that the electron donating 4-substituted sulfonyl derivatives (9a, 9b, 9c, and 9e) on the nitrogen atom of the morpholine ring increases the affinity of M1 receptor binding 50- to 80-fold greater than the corresponding arecoline. Other derivatives also showed considerable M1 receptor binding affinity

(Z)-3-(3,4-dimethoxyphenyl)-2-(4-methoxyphenyl)acrylonitrile

A new dipolarophile used in the construction of bioactive heterocycles, (Z)-3-(3,4-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile, C18H17NO3, has been synthesized by base-catalysed reaction of 3,4-dimethoxybenzaldehyde with (4-methoxyphenyl) acetonitrile. The olefinic bond has Z geometry and the molecules are linked by C-H center dot center dot center dot O and C-H center dot center dot center dot N hydrogen bonds.