Synthesis, Biological Evaluation and in Silico Studies of 3-Hydroxy-N-(2-(substituted phenyl)-4-oxothiazolidin-3-yl)-2-napthamide Derivatives.

In the present study, a series of 3-hydroxy-N-(2-(substituted phenyl)-4-oxothiazolidin-3-yl)-2-napthamide derivatives were synthesized, characterized and evaluated for theirin vitroactivity, i. e., antimicrobial, antioxidant and anti-inflammatory. The target compounds were synthesized by condensation reaction of 3-hydroxy-2-naphthoic acid hydrazide with substituted benzaldehydes which were subjected to cyclization reaction with thioglycolic acid and ZnCl2 to get target compounds. The synthesized 3-hydroxy-N-(2-(substituted phenyl)-4-oxothiazolidin-3-yl)-2-napthamide derivatives were examined for their antimicrobial activity and 3-hydroxy-N-(4-oxo-2-(3,4,5-trimethoxyphenyl)thiazolidin-3-yl)-2-naphthamide (S20) exhibited the highest antimicrobial potential. The N'-(2,3-dichlorobenzylidene)-3-hydroxy-2-naphthohydrazide (S5) displayed good antifungal potential against Rhizopus oryzae, whereas N'-(2,3-dichlorobenzylidene)-3-hydroxy-2-naphthohydrazide (S20) showed the highest antioxidant potential and N-(2-(2,6-dichlorophenyl)-4-oxothiazolidin-3-yl)-3-hydroxy-2-naphthamide (S16) displayed the highest anti-inflammatory activity. The results of molecular docking studies revealed that existence of hydrogen bonding and hydrophobic interactions with their respective proteins. In silico ADMET studies were carried out by Molinspiration, Pre-ADMET and OSIRIS property explorer to predict the pharmacokinetic behaviour of synthesized 3-hydroxy-N-(2-(substituted phenyl)-4-oxothiazolidin-3-yl)-2-napthamide derivatives.

Alzheimer's disease: Molecular aspects and treatment opportunities using herbal drugs.

Alzheimer's disease (AD), also called senile dementia, is the most common neurological disorder. Around 50 million people, mostly of advanced age, are suffering from dementia worldwide and this is expected to reach 100-130 million between 2040 and 2050. AD is characterized by impaired glutamatergic and cholinergic neurotransmission, which is associated with clinical and pathological symptoms. AD is characterized clinically by loss of cognition and memory impairment and pathologically by senile plaques formed by Amyloid ß deposits or neurofibrillary tangles (NFT) consisting of aggregated tau proteins. Amyloid ß deposits are responsible for glutamatergic dysfunction that develops NMDA dependent Ca2+ influx into postsynaptic neurons generating slow excitotoxicity process leading to oxidative stress and finally impaired cognition and neuronal loss. Amyloid decreases acetylcholine release, synthesis and neuronal transport. The decreased levels of neurotransmitter acetylcholine, neuronal loss, tau aggregation, amyloid ß plaques, increased oxidative stress, neuroinflammation, bio-metal dyshomeostasis, autophagy, cell cycle dysregulation, mitochondrial dysfunction, and endoplasmic reticulum dysfunction are the factors responsible for the pathogenesis of AD. Acetylcholinesterase, NMDA, Glutamate, BACE1, 5HT6, and RAGE (Receptors for Advanced Glycation End products) are receptors targeted in treatment of AD. The FDA approved acetylcholinesterase inhibitors Donepezil, Galantamine and Rivastigmine and N-methyl-D-aspartate antagonist Memantine provide symptomatic relief. Different therapies such as amyloid ß therapies, tau-based therapies, neurotransmitter-based therapies, autophagy-based therapies, multi-target therapeutic strategies, and gene therapy modify the natural course of the disease. Herbal and food intake is also important as preventive strategy and recently focus has also been placed on herbal drugs for treatment. This review focuses on the molecular aspects, pathogenesis and recent studies that signifies the potential of medicinal plants and their extracts or chemical constituents for the treatment of degenerative symptoms related to AD.

Synthesis, in silico studies and biological screening of (E)-2-(3-(substitutedstyryl)-5-(substitutedphenyl)-4,5-dihydropyrazol-1-yl)benzo[d]thiazole derivatives as an anti-oxidant, anti-inflammatory and antimicrobial agents.

A new series of (E)-2-(3-(substitutedstyryl)-5-(substitutedphenyl)-4,5-dihydropyrazol-1-yl)benzo[d]thiazole derivatives was synthesized and the chemical structures of synthesized compounds were deduced by IR and NMR spectral tools. These compounds were synthesized via aldol condensation reaction of substituted benzaldehydes and acetone in alkaline ethanolic solution and their in vitro anti-oxidant, anti-inflammatory and antimicrobial activities were investigated. All the synthesized compounds displayed anti-oxidant potential with IC50 values ranging from 0.13 to 8.43 µmol/ml. The compound Z13 exhibited potent anti-inflammatory activity with IC50 value of 0.03 µmol/ml compared with the standard ibuprofen, which showed IC50 value of 0.11 µmol/ml. On the other hand, most of the compounds had a certain antibacterial potential particularly against P. aeruginosa and among these derivatives, compound Z2 exhibited the highest potential against P. aeruginosa with MIC value of 0.0069 µmol/ml. The analysis of docking results demonstrated the binding affinity and hydrogen bond, electrostatic and hydrophobic interactions of all the synthesized compounds with their respective targets. In silico ADMET studies were carried out for the synthesized compounds and most of the compounds exhibited good ADMET profile.

Synthesis and Biological Evaluation of 2-(Halophenyl)benzoxazole-5-Carboxylic Acids as Potential Anti-Inflammatory and Cytotoxic Agent with Molecular Docking Studies.

2-Halogenatedphenyl benzoxazole-5-carboxylic acids with mono-halogen (chloro, bromo and fluoro) substituted at ortho-, meta- and para-positions on the phenyl ring were designed and synthesized based on significance of presence of halogen in increasing number of marketed halogenated drugs and importance of benzoxazoles. These 2-alogenatedphenylbenzoxazole-5-carboxylic acids and their methyl esters were screened for anti-inflammatory activity, and cytotoxicity. 2-(3-Chlorophenyl)benzoxaole-5-carboxylic acid (6b) exhibited significant anti-inflammatory activity with IC50 values of 0.103 mM almost equivalent to the standard drug ibuprofen (0.101 mM). 2-(4-Chlorophenyl)benzoxaole-5-carboxylic acid (6c) showed excellent cytotoxic activity against 22Rv1 cells (human prostate carcinoma epithelial cell lines) with IC50 value of 1.54 µM better than that of standard drug doxorubicin having IC50 value of 2.32 µM. More importantly, the selectivity index of this potential molecule was found to be 57.74. Molecular docking analysis resulted in good binding interactions of these compounds with their respective biochemical targets viz. Cyclooxygenase-2 and aldo-keto reductase IC3.

Synthesis, Biological Activity and Molecular Docking Studies of Heterocyclic Chalcones.

Nineteen heterocyclic chalcones were synthesized from 4-acetyl-5-methylquinolylpyrazole and heteroaryl (imidazole, pyrazole, thiophene, indole and triazole) aldehydes and were screened in vitro using four tumor cell lines for their cytotoxic capability and for antimicrobial activity. The chalcone 5b exhibited the highest activity with IC50 values 2.14 µM against colon (HCT-116) and 5.0 µM, against prostate (PC-3) cancer cell lines and also displayed good activity against fungal strain (A. niger) with MIC value 9.1 µM. The chalcones 5q and 5p displayed good activity against bacterial strains (S. aureus) having MIC value 2.6 µM and fungal strain (C. albicans) having MIC value 5.4 µM, respectively. The molecular docking outcome revealed that the synthesized heterocyclic chalcones demonstrated hydrogen bond, hydrophobic and electrostatic interactions with their respective biochemical targets.

Synthesis, molecular docking and molecular dynamic simulation studies of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives as antidiabetic agents.

A series of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives (5a-5v) has been synthesized and confirmed by physicochemical(Rf, melting point) and spectral means (IR, 1HNMR, 13CNMR). The results of in vitro antidiabetic study against α-glucosidase indicated that compound 5o bearing 2-CH3-5-NO2 substituent on phenyl ring was found to be the most active compound against both enzymes. The electron donating (CH3) group and electron withdrawing (NO2) group on a phenyl ring highly favoured the inhibitory activity against these enzymes. The docking simulations study revealed that these synthesized compounds displayed hydrogen bonding, electrostatic and hydrophobic interactions with active site residues. The structure activity relationship studies of these compounds were also corroborated with the help of molecular modeling studies. Molecular dynamic simulations have been done for top most active compound for validating its α-glucosidase and α-amylase inhibitory potential, RMSD analysis of ligand protein complex suggested the stability of top most active compound 5o in binding site of target proteins. In silico ADMET results showed that synthesized compounds were found to have negligible toxicity, good solubility and absorption profile as the synthesized compounds fulfilled Lipinski's rule of 5 and Veber's rule.

2,4-Dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic Acid Derivatives: In Vitro Antidiabetic Activity, Molecular Modeling and In silico ADMET Screening.

BACKGROUND: Postprandial hyperglycemia can be reduced by inhibiting major carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase which is an effective approach in both preventing and treating diabetes. OBJECTIVE: The aim of this study was to synthesize a series of 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl] benzoic acid derivatives and evaluate α-glucosidase and α-amylase inhibitory activity along with molecular docking and in silico ADMET property analysis. METHOD: Chlorosulfonation of 2,4-dichloro benzoic acid followed by reaction with corresponding anilines/amines yielded 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic acid derivatives. For evaluating their antidiabetic potential α-glucosidase and α-amylase inhibitory assays were carried out. In silico molecular docking studies of these compounds were performed with respect to these enzymes and a computational study was also carried out to predict the drug-likeness and ADMET properties of the title compounds. RESULTS: Compound 3c (2,4-dichloro-5-[(2-nitrophenyl)sulfamoyl]benzoic acid) was found to be highly active having 3 fold inhibitory potential against α-amylase and 5 times inhibitory activity against α-glucosidase in comparison to standard drug acarbose. CONCLUSION: Most of the synthesized compounds were highly potent or equipotent to standard drug acarbose for inhibitory potential against α-glucosidase and α-amylase enzyme and hence this may indicate their antidiabetic activity. The docking study revealed that these compounds interact with active site of enzyme through hydrogen bonding and different pi interactions.