Vipin Saini

Schiff Bases: A Versatile Pharmacophore

Schiff bases are condensation products of primary amines with carbonyl compounds gaining importance day by day in present scenario. Schiff bases are the compounds carrying imine or azomethine (–C=N–) functional group and are found to be a versatile pharmacophore for design and development of various bioactive lead compounds. Schiff bases exhibit useful biological activities such anti-inflammatory, analgesic, antimicrobial, anticonvulsant, antitubercular, anticancer, antioxidant, anthelmintic, antiglycation, and antidepressant activities. Schiff bases are also used as catalysts, pigments and dyes, intermediates in organic synthesis, polymer stabilizers, and corrosion inhibitors. The present review summarizes information on the diverse biological activities and also highlights the recently synthesized numerous Schiff bases as potential bioactive core.

Formulation and Characterization of Drug Loaded Nonionic Surfactant Vesicles (Niosomes) for Oral Bioavailability Enhancement

Nonionic surfactant vesicles (niosomes) were formulated with an aim of enhancing the oral bioavailability of tenofovir disoproxil fumarate (TDF), an anti-HIV drug. Niosomes were formulated by conventional thin film hydration technique with different molar ratios of surfactant, cholesterol, and dicetyl phosphate. The formulated niosomes were found spherical in shape, ranging from 2.95 μm to 10.91 μm in size. Vesicles with 1 : 1 : 0.1 ratios of surfactant : cholesterol : dicetyl phosphate with each grade of span were found to have higher entrapment efficiencies, which were further selected for in vitro and in vivo studies. Vesicles formulated with sorbitan monostearate were found to have maximum drug release (99.091%) at the end of 24 hours and followed zero order release kinetics. The results of in vivo study revealed that the niosomes significantly enhanced the oral bioavailability of TDF in rats after a dose of 95 mg/kg. The average relative bioavailability of niosomes in relation to plane drug solution was found to be 2.58, indicating more than twofold increase in oral bioavailability of TDF. Significant increase in mean residential time (MRT) was also found, reflecting release retarding efficacy of the vesicles. In conclusion, niosomes could be a promising delivery for TDF with improved oral bioavailability and prolonged release profiles.

Mannich bases: an important pharmacophore in present scenario.

Mannich bases are the end products of Mannich reaction and are known as beta-amino ketone carrying compounds. Mannich reaction is a carbon-carbon bond forming nucleophilic addition reaction and is a key step in synthesis of a wide variety of natural products, pharmaceuticals, and so forth. Mannich reaction is important for the construction of nitrogen containing compounds. There is a number of aminoalkyl chain bearing Mannich bases like fluoxetine, atropine, ethacrynic acid, trihexyphenidyl, and so forth with high curative value. The literature studies enlighten the fact that Mannich bases are very reactive and recognized to possess potent diverse activities like anti-inflammatory, anticancer, antifilarial, antibacterial, antifungal, anticonvulsant, anthelmintic, antitubercular, analgesic, anti-HIV, antimalarial, antipsychotic, antiviral activities and so forth. The biological activity of Mannich bases is mainly attributed to α, β-unsaturated ketone which can be generated by deamination of hydrogen atom of the amine group.

Therapeutic potential of hydrazones as anti-inflammatory agents.

Hydrazones are a special class of organic compounds in the Schiff base family. Hydrazones constitute a versatile compound of organic class having basic structure (R1R2C=NNR3R4). The active centers of hydrazone, that is, carbon and nitrogen, are mainly responsible for the physical and chemical properties of the hydrazones and, due to the reactivity toward electrophiles and nucleophiles, hydrazones are used for the synthesis of organic compound such as heterocyclic compounds with a variety of biological activities. Hydrazones and their derivatives are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal, anti-HIV, and so forth. The present review summarizes the efficiency of hydrazones as potent anti-inflammatory agents.

Design, characterization, computational studies, and pharmacological evaluation of substituted-N′-[(1E) substituted-phenylmethylidene]benzohydrazide analogs

A series of substituted-N′-[(1E)-substituted-phenylmethylidene]benzohydrazide analogs were synthesized and authenticated by TLC, UV–Visible, FTIR, and NMR spectroscopic techniques. The physicochemical similarity of the new analogs with standard drugs was assessed by calculating from a set of ten physicochemical properties using software programs. The information so obtained can be related to prediction of biological activity for important targets. All the target compounds 4a–n were evaluated for their antioxidant, anti-inflammatory, and antimicrobial activity using different in vitro models. The test compounds demonstrated good similarity values with respect to the standard drugs. The compounds 4c, 4d, and 4e have emerged as important lead compounds showing potential anti-inflammatory; and 4b, 4f, and 4c having antioxidant profile. While studying MIC against bacterial strains 4c, 4f, 4i, 4k, and 4m were most active among all the target compounds. All compounds were found to have very good antifungal activity. The compounds having nitro substitution at the arylidene moiety i.e., 4c and 4f showed the most potent antifungal as well as antibacterial activities. While studying total antioxidant activity, all target compounds were found to have good antioxidant activity.

1,4-Diaryl-2-mercaptoimidazoles derivatives as a novel class of antimicrobial agents: design, synthesis, and computational studies

In search of a new class of potential antimicrobial agents, some 1,4-diaryl-2-mercaptoimidazoles (5a–5h) were prepared by employing a mild and green approach in which substituted anilines 3 were treated with phenacylbromide 2 in the presence of Na2CO3/K2CO3 followed by the treatment of a solid catalyst, p-TSA (para toluene sulphonic acid), to give imidazole derivatives in excellent yields. All compounds were characterized on the basis of their UV, IR, 1H & 13C NMR, and Mass spectral data. Pharmacotherapeutic potential with the possible molecular mechanism of action of the compounds were estimated on the basis of prediction of activity spectra for substances (PASS) prediction results obtained by PharmaExpert software. The activity profile predicted by PASS was further supported by some theoretical calculations, in vitro experimental evaluation, and then validated via docking studies. In vitro antimicrobial potential was evaluated via agar well diffusion assay against five bacterial strains (one Gram-positive and four Gram-negative bacteria) and two pathogenic fungi. The antibacterial activity of the test compounds 5a–h against P. aeruginosa was found to be similar to that of Ceftriaxone, an efficient second generation antibiotic. Compound 5h displayed promising broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacterial strains. Except 4e, almost all the compounds were found to have an excellent level of antifungal activity against C. albicans when compared with a standard drug, Fluconazole. The docking results obtained confirm the interactions of compounds (5a–h) with the active site of cytochrome P450 14 α-sterol demethylase. Thus, it is concluded that the compounds considered under this investigation have an excellent potential to be acted, as antimicrobial leads in the future medicinal chemistry.

Anti-Inflammatory, Analgesic Evaluation and Molecular Docking Studies of N-Phenyl Anthranilic Acid-Based 1,3,4-Oxadiazole Analogues

A novel series of N-phenyl anthranilic acid-based 1,3,4-oxadiazoles were prepared (4a–h) and subjected to anti-inflammatory, analgesic activity and molecular docking studies to target cyclooxygenase-2 enzyme. 1,3,4-Oxadiazole derivatives were screened for anti-inflammatory activity in carrageenan-induced rat paw edema and analgesic activity by tail immersion method. In synthesized compounds, the free carboxylic group, which is responsible for gastric side effects, was derivatized by heterocyclic 1,3,4-oxadiazole bioactive core, which showed good interaction with COX-2 receptor with good docking score. Among all the synthesized compounds, 4e and 4f have emerged out as potential COX-2 inhibitors.

Synthesis, characterization, and computational studies on phthalic anhydride-based benzylidene-hydrazide derivatives as novel, potential anti-inflammatory agents

A series of phthalic anhydride-based substituted benzylidene-hydrazide derivatives (3a–i) was synthesized. The synthesized derivatives were authenticated by TLC, UV–visible, FTIR, NMR, and mass spectroscopic techniques and further screened for in vivo anti-inflammatory and analgesic activities by carrageenan-induced rat paw oedema and tail immersion methods, respectively, using diclofenac sodium as standard drug. The derivatives 3d, 3e, and 3h were found to be most active anti-inflammatory and analgesic agents among all the synthesized derivatives. The physico-chemical similarity of the derivatives with standard drugs was assessed by calculating various physicochemical properties using software programs. The percent similarity of synthesized derivatives was found to be good except 3i. The derivatives were subjected to QSAR by multilinear regression using Analyze it version 3.0 software and two statistically sound models were developed with R2 (0.933–0.960),

Design and synthesis of new 2,5-disubstituted-1,3,4-oxadiazole analogues as anticancer agents

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