Synthesis, Molecular Docking and Evaluation of 3-{4-[2-amino-4-(substitutedphenyl)-2H-[1, 3] oxazin/thiazin-6-yl} 2-phenyl-3H-quinazolin-4-one Derivatives for their Anticonvulsant Activity.

BACKGROUND: According to the WHO, around 50 million people worldwide are suffering from epilepsy. It is due to the repeated occurring of seizures. These seizures are caused by sudden which may vary from a brief lapse of attention or muscle jerks, to severe and prolonged convulsions. OBJECTIVES: The aim of the present work was to synthesize 2-phenyl substituted quinazolinone derivatives and to evaluate them for anticonvulsant and neurotoxic activity. METHODS: A series of novel 3-{4-[2-amino-4-(substitutedphenyl)-2H-[1.3] oxazin/thiazin-6-yl} 2- phenyl-3H-quinazolin-4-one derivatives were synthesized and evaluated for their anticonvulsant activity. The structures of the compound have been confirmed by spectral analysis. The molecular docking was performed for all the synthesized compounds to assess their binding mode to Gamma- aminobutyric acid type A (GABAA) receptor in order to rationalize their anticonvulsant activities in a qualitative way. Anticonvulsant activities of compounds were screened by using (Maximal electroshock) MES induced seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in Wistar rats of either sex. None of the compounds demonstrated any sign of neurotoxicity. RESULT: Compounds 3-{4-[2-amino-4-(4-nitro-phenyl)-2H-[1, 3] oxazin-6-yl} 2-phenyl-3H-quinazolin- 4-one (5a) have shown significant activity against tonic seizure by the MES model and 3-{4-[2-amino- 4-(4-nitro-phenyl)-2H-[1, 3] thiazin-6-yl} 2-phenyl-3H-quinazolin-4-one (5d) against clonic seizure by scPTZ induced seizure model. CONCLUSION: All the newly synthesized compounds had significant anticonvulsant activity. The same two compounds 5a and 5d showed promising activity, while the other compounds have moderate activity. The proposed work is to effort towards the development and identification of novel molecules as anticonvulsant agents by the synthesis of some novel quinazolinone derivatives with improved biological activity.

Hansch Analysis of Novel Acetamide Derivatives as Highly Potent and Specific MAO-A Inhibitors.

BACKGROUND: A quantitative structure-activity relationship (QSAR) study of novel Acetamide derivatives as specific Mono amino oxidase (MAO) A inhibitory agents was performed with 28 compounds to derive QSAR models for better activity and lesser side effects. METHODS: Various thermodynamic, electronic and steric parameters were calculated using Chem 3D package of molecular modeling software Chemoffice 7.0. QSAR models were generated employing sequential multiple regression method using in-house statistical program VALSTAT. The best models were selected from the various statistically significant equations. RESULTS: The study revealed that an increase in the bulkiness of the substituent's and molecular solvent accessible surface area is beneficial to the biological activity and the substitution of two interacting groups should be separated by more than three atoms will give better biological activity. Model also suggests that the presence of the comparatively less lipophilic group may increase MAO-A inhibitory activity and substituent that decrease the flexibility and increase rigidity of the nucleus will enhance the activity. The best QSAR model was selected, having a correlation coefficient (r) = 0.93271, coefficient of determination (r2) = 0.8509 with a standard deviation of predictivity (SDEP) = 0.31287 and cross validated squared correlation coefficient (Q2) = 0.92. The predictive ability of the selected model was also confirmed by leave one out cross validation and r2 predicted (r2 pred) was 0.764. CONCLUSION: This study may be useful in the designing of more potent substituted acetamide derivatives as specific MAOA inhibitors.

Synthetic and Natural Monoamine Oxidase Inhibitors as Potential Lead Compounds for Effective Therapeutics.

Monoamine oxidases A and B (MAO-A and B) play a critical role in the metabolism of intracellular neurotransmitters of the central nervous system. For decades, MAO inhibitors have proven their clinical efficacy as potential drug targets for several neurological and neurodegenerative diseases. Use of first generation non selective MAO inhibitors as neuropsychiatric drugs elicited several side effects like hypertensive crisis and cheese reaction. Therefore their use is now limited due to non-selectivity towards MAO isoforms and inhibition of metabolizing enzymes like cytochrome P450. Development of selective and specific MAO inhibitors like moclobemide, toloxatone improves their efficacy as disease-modifying effects in monotherapy as well as adjunctive therapy. Recently a lot of research has been done to elucidate the pharmacological potential of medicinal plants and their isolated bioactive constituents having MAO inhibitory activity. Herbs containing MAO inhibitors are extensively used for the development of potent synthetic drugs and as safe and effective alternatives to the available synthetic drugs in the treatment of neurodegenerative diseases such as depression, Parkinson and Alzheimer's. In several diseases like Parkinson natural MAO inhibitors prevented the neuron denaturalization by their dual action via enhancing neurotransmission of dopamine as well as lowering the generation of free radicals and toxins. Currently development of selective MAO inhibitors is still under study to achieve more effective therapies by using Computer Aided Drug Designing, Ligand-based models and structure-activity hypothesis. These approaches also facilitate understanding the interaction of newly designed molecule with MAO enzymes and the rationalization of probable mechanisms of action.

In-vitro cytotoxicity study of methanolic fraction from Ajuga Bracteosa wall ex. benth on MCF-7 breast adenocarcinoma and hep-2 larynx carcinoma cell lines.

OBJECTIVE: Ajuga bracteosa Wall ex Benth (Labiatae) is popularly known in India as Neelkanthi. A decoction of the leaves, flowers, and barks is used in India for the treatment of cancer including diabetes, malaria, and inflammation etc. The main objective of this study is to investigate the cytotoxic potential of Ajuga bracteosa. MATERIALS AND METHODS: Successive solvent extraction of Ajuga bracteosa in petroleum ether, methanol, and water extracts was done. These extracts were tested against human breast adenocarcinoma (MCF-7) and larynx carcinoma (Hep-2) tumor cell lines, using the thiazolyl blue test (MTT) assay. RESULTS: The methanolic fraction of Ajuga bracteosa had shown the significant results against MCF-7 and Hep-2 tumor cell lines. The methanolic, petroleum ether and aqueous extract from Ajuga bracteosa, presented an IC50 value at 24 h of 10, 65, 70 µg/ml and 5, 30, 15 µg/ml on MCF-7 and Hep-2 cells, respectively. Steroids compounds namely ß-sitosterol and unknown constituents were identified in the most active methanol extract of Ajuga bracteosa wall ex Benth. These known and unknown compounds exhibited cytotoxic potential against MCF-7 and Hep-2 cancer cells. CONCLUSION: Among all the tested extracts, methanolic extract can be considered as potential sources of anti-cancer compounds. Further studies are necessary for more extensive biological evaluations.

Wound healing activity of Sida cordifolia Linn. in rats.

INTRODUCTION: The present study provides a scientific evaluation for the wound healing potential of ethanolic (EtOH) extract of Sida cordifolia Linn. (SCL) plant. MATERIALS AND METHODS: Excision, incision and burn wounds were inflicted upon three groups of six rats each. Group I was assigned as control (ointment base). Group II was treated with 10% EtOH extract ointment. Group III was treated with standard silver sulfadiazine (0.01%) cream. The parameters observed were percentage of wound contraction, epithelialization period, hydroxyproline content, tensile strength including histopathological studies. RESULT: It was noted that the effect produced by the ethanolic extract of SCL ointment showed significant (P < 0.01) healing in all wound models when compared with the control group. All parameters such as wound contraction, epithelialization period, hydroxyproline content, tensile strength and histopathological studies showed significant (P < 0.01) changes when compared with the control. CONCLUSION: The ethanolic extract ointment of SCL effectively stimulates wound contraction; increases tensile strength of excision, incision and burn wounds.

Wound healing potential of methanolic extract of Trichosanthes dioica Roxb (fruits) in rats.

AIM OF THE STUDY: The present study provides a scientific evaluation for the wound healing potential of methanolic (MeOH) extract of TDR fruits. MATERIALS AND METHODS: Excision and incision wounds were inflicted upon three groups of six rats each. Group I was assigned as control (ointment base), Group II was treated with standard silver sulfadiazine (0.01%) cream. Group III was treated with 5% MeOH extract ointment. The parameters observed were percentage of wound contraction, epithelialization period, hydroxyproline content, tensile strength including histopathological studies. RESULTS: It was noted that the effect produced by the extract ointment showed significant (P<0.01) healing in both the wound models when compared with control group. All parameters such as wound contraction, epithelialization period, hydroxyproline content, tensile strength and histopathological studies showed significant changes when compared to control. CONCLUSION: The result shows that TDR extract ointment demonstrates wound healing potential in both excision and incision models.