Sandhya Bawa

Biological Activities of Quinoline Derivatives

Quinoline and its fused heterocyclic derivatives tested with diverse pharmacological activity functional groups constitute an important class of compounds for new drug development. Therefore, many researchers have synthesized these compounds as target structures and evaluated their biological activities. The present review provides an in depth view of work done so far on quinolines and its biological activities covering anticancer, antimycobacterial, antimicrobial, anticonvulsant, antiinflamatory and cardiovascular activities.

A review on anticancer potential of bioactive heterocycle quinoline

The advent of Camptothecin added a new dimension in the field anticancer drug development containing quinoline motif. Quinoline scaffold plays an important role in anticancer drug development as their derivatives have shown excellent results through different mechanism of action such as growth inhibitors by cell cycle arrest, apoptosis, inhibition of angiogenesis, disruption of cell migration, and modulation of nuclear receptor responsiveness. The anti-cancer potential of several of these derivatives have been demonstrated on various cancer cell lines. In this review we have compiled and discussed specifically the anticancer potential of quinoline derivatives, which could provide a low-height flying birds eye view of the quinoline derived compounds to a medicinal chemist for a comprehensive and target oriented information for development of clinically viable anticancer drugs.

Biological Activities of Pyrazoline Derivatives -A Recent Development

Pyrazolines are well known and important nitrogen containing 5-membered heterocyclic compounds and various methods have been worked out for their synthesis. Numerous pyrazoline derivatives have been found to possess considerable biological activities, which stimulated the research activity in this field. They have several prominent effects, such as antimicrobial, antimycobacterial, antifungal, antiamoebic, anti-inflammatory, analgesic, antidepressant and anticancer activities. They also possess some potent receptor selective biological activity like Nitric oxide synthase (NOS) inhibitor and Cannabinoid CB1 receptor antagonists activity. 4,5-dihydro-1H- pyrazolines seem to be the most frequently studied pyrazoline type compounds. As a result, a large number of such pyrazolines using different synthetic methods for their preparation have been described in the chemistry literature. The present review provides an insight view to pyrazolines synthesis and its biological activities along with the compilation of recent patents on pyrazolines.

Synthesis and pharmacological evaluation of pyrazolo[4,3-c]cinnoline derivatives as potential anti-inflammatory and antibacterial agents.

A series of pyrazolo[4,3-c]cinnoline derivatives was synthesized, characterized and evaluated for anti-inflammatory and antibacterial activity. Test compounds that exhibited good anti-inflammatory activity were further screened for their ulcerogenic and lipid peroxidation activity. Compounds 4d and 4l showed promising anti-inflammatory activity with reduced ulcerogenic and lipid peroxidation activity when compared to naproxen. Docking results of these two compounds with COX-2 (PDB ID: 1CX2) also exhibited a strong binding profile. Among the test derivatives, compound 4i displayed significant antibacterial property against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. However, compound 4b emerged as the best dual anti-inflammatory-antibacterial agent in the present study.

Antidepressant potential of nitrogen-containing heterocyclic moieties: An updated review

Depression is currently the fourth leading cause of disease or disability worldwide. Antidepressant is approved for the treatment of major depression (including paediatric depression), obsessive-compulsive disorder (in both adult and paediatric populations), bulimia nervosa, panic disorder and premenstrual dysphoric disorder. Antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. Many drugs produce an antidepressant effect, but restrictions on their use have caused controversy and off-label prescription a risk, despite claims of superior efficacy. Our current understanding of its pathogenesis is limited and existing treatments are inadequate, providing relief to only a subset of people suffering from depression. Reviews of literature suggest that heterocyclic moieties and their derivatives has proven success in treating depression.

Syntheses and evaluation of anti-inflammatory, analgesic and ulcerogenic activities of 1,3,4-oxadiazole and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives

Several 2,5-disubstituted-1,3,4-oxadiazoles (4a–f) and 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles (7a–f) were synthesized and characterized by elemental analyses and spectral data. These compounds were screened for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities. Compound 7c showed excellent anti-inflammatory and remarkable analgesic activity with reduced ulcerogenic and lipid peroxidation activity when compared with ibuprofen.

Synthesis and antimicrobial activity of 2-chloro-6-methylquinoline hydrazone derivatives

Purpose : A series of 2-chloro-6-methylquinoline hydrazones (3a-o) were synthesized by the condensation of substituted acyl hydrazines, semicarbazide, thiosemicarbazide, and INH with 2-chloro-3-formyl-6-methylquinoline in absolute alcohol and were tested for antimicrobial activity. Materials and Methods : The structures of compounds were established using modern analytical technique FT-IR, 1 H and 13 C-NMR, mass spectral data and elemental analysis. All the compounds were evaluated for their antibacterial activity against Escherichia coli (NCTC 10418), Staphylococcus aureus (NCTC 65710), and Pseudomonas aeruginosa (NCTC 10662). The compounds were also tested for antifungal activity aganist Aspergillus niger (MTCC 281), Aspergillus flavus (MTCC 277), Monascus purpureus (MTCC 369) and Penicillium citrinum (NCIM 768) by the cup-plate method. Results : It was observed that maximum antibacterial activity was shown by compounds having the 4-fluoro, 4-chloro, 4-nitro, and 2, 4-dicloro group in the benzoyl ring. Compounds were weakly active against fungal strains. Conclusion : Quinolinyl hydrazone of INH 3o was found to be most active toward the bacterial strains compared to their corresponding benzoyl derivatives.

2-Benzamido-4-methylthiazole-5-carboxylic Acid Derivatives as Potential Xanthine Oxidase Inhibitors and Free Radical Scavengers

The new chemical entities febuxostat and topiroxostat have been approved by the US Food and Drug Administration, opening new avenues for exploiting different heterocycles other than purines as xanthine oxidase (XO) inhibitors. A different series of substituted 2‐benzamido‐4‐methylthiazole‐5‐carboxylic acid derivatives (5a–r) was synthesized and characterized by the collective use of IR, 1H and 13C NMR, and mass spectroscopy, for the treatment of gout and hyperuricemia. In vitro studies of the synthesized derivatives revealed that the presence of a fluoro group at the para position in 5b (IC50 = 0.57 μm) and a chloro group in 5c (IC50 = 0.91 μm) signifies excellent XO inhibitory activity among the series, along with their DPPH free radial scavenging activity. In vivo serum uric acid inhibition studies established that 5b and 5c displayed 62 and 53% uric acid inhibition, respectively. Studies on enzyme kinetics indicated that 5b acts as a mixed type inhibitor. In silico prediction by various softwares also helped in the recognition of potent XO inhibitors.

Docking based virtual screening and molecular dynamics study to identify potential monoacylglycerol lipase inhibitors.

Monoacylglycerol lipase (MAGL) is one of the key enzymes of the endocannabinoid system (ECS). It hydrolyzes one of the major endocannabinoid, 2-arachidonoylglycerol (2-AG), an endogenous full agonist at G protein coupled cannabinoid receptors CB1 and CB2. Numerous studies showed that MGL inhibitors are potentially useful for the treatment of pain, inflammation, cancer and CNS disorders. These provocative findings suggested that pharmacological inhibition of MAGL function may confer significant therapeutic benefits. In this study, we presented hybrid ligand and structure-based approaches to obtain a novel set of virtual leads as MAGL inhibitors. The constraints used in this study, were Glide score, binding free energy estimates and ADME properties to screen the ZINC database, containing approximately 21 million compounds. A total of seven virtual hits were obtained, which showed significant binding affinity towards MAGL protein. Ligand, ZINC24092691 was employed in complex form with the protein MAGL, for molecular dynamics simulation study, because of its excellent glide score, binding free energy and ADME properties. The RMSD of ZINC24092691 was observed to stay at 0.1 nm (1 Å) in most of the trajectories, which further confirmed its ability to inhibit the protein MAGL. The hits were then evaluated for their ability to inhibit human MAGL. The compound ZINC24092691 displayed the noteworthy inhibitory activity reducing MAGL activity to 21.15% at 100 nM concentration, with an IC50 value of 10 nM.

2-[(4-Chlorobenzyl) amino]-4-methyl-1,3-thiazole-5-carboxylic acid exhibits antidiabetic potential and raises insulin sensitivity via amelioration of oxidative enzymes and inflammatory cytokines in streptozotocin˗induced diabetic rats

Thiazole derivatives are potential candidates for drug development. They can be efficiently synthesized and are extremely active against several diseases, including diabetes. In our present study, we investigated the anti-diabetic, anti-oxidant and anti-inflammatory properties of 2-[(4-Chlorobenzyl) amino]-4-methyl-1,3-thiazole-5-carboxylic acid (BAC) a new thiazole derivative, in a streptozotocin (STZ) induced neonatal model of non-insulin dependent diabetes mellitus (NIDDM) rats. Diabetes was induced by injecting STZ (100mg/kg) intraperitoneally to two days old pups. BAC administration for 3 weeks significantly decreased blood glucose and raised insulin level and improves insulin sensitivity (KITT) level. Additionally, BAC also suppressed several inflammatory cytokines generation as evidenced by decreased levels of serum tumor necrosis factor-α and interleukin-6. In addition, BAC also protects against hyperlipidemia and liver injury. Furthermore, BAC significantly restored pancreatic lipid peroxidation, catalase, superoxide dismutase, and reduced glutathione content. Histological studies of pancreatic tissues showed normal architecture after BAC administration to diabetic rats. Altogether, our results suggest that BAC successfully reduces the blood glucose level and possesses anti-oxidant as well as anti-inflammatory activity. This leads to decreased histological damage in diabetic pancreatic tissues suggesting the possibility of future diabetes treatments.