Pharmacological Evaluation of Novel Pyridine and Fluorene Derivatives for their Cytotoxicity, Antioxidant, Antimicrobial and Antidiabetic activities: Both In Vivo and In Vitro Analyses

Abstract

The occurrence of various diseases poses a great threat to human health since ages. Due to association of various side effects with the already available drugs, novel drugs are required having better safety and efficacy. Screening of lead compounds is a continuous process for determination of novel compounds with better profile. For the screening process, biological activities of newly synthesized compounds are measured utilizing bioassays. In the present study, novel pyridine (BVPP and DNP) and fluorene derivatives (BDFPF) were screened for the determination of various in vitro and in vivo biological activities. In the in vitro study, cytotoxicity (brine shrimp cytotoxicity assay and hemolytic assay), antioxidant (DPPH free radical scavenging assay, iron-chelating assay, and reducing power assay and nitric oxide scavenging assay and total antioxidant assay), antimicrobial (antibacterial and antifungal), anti inflammatory (Protein denaturation assay), and enzyme inhibition (α-amylase and α glucosidase inhibition assays) activity was measured. In the in vivo study, anti inflammatory (carrageenan-induced paw oedema assay), analgesic (Hot plate analgesic assay), anti-coagulant, anti-depressant (tail suspension method) and antidiabetic activity was measured. In the antidiabetic assay, blood glucose concentration, total protein, antioxidant enzymes level (catalase, super oxide dismutase and glutathione), and oxidative stress markers level (lipid peroxidation, hydrogen peroxide and sodium nitrite) in tissue homogenates of the pancreas, heart, kidney and liver were measured. Moreover, the effect of compounds on these organs against alloxan-induced tissue damage was assessed by histopathological analysis. Results of in vitro assays indicated that these compounds were found to be non-toxic and cyto-compatible. DPPH, iron chelating and total antioxidant activity was not shown by any of these compounds. Reducing power activity was shown by fluorene derivative (BDFPF). Nitric oxide scavenging activity was shown by both pyridine (BVPP and DNP) and fluorene derivatives (BDFPF). These compounds showed no antimicrobial and anti-inflammatory activities. BVPP showed α-amylase and DNP showed α-glucosidase inhibition activity. BVPP and BDFPF were subjected to in vivo assays due to non-toxic behavior, and found to have good anti-inflammatory, analgesic, anticoagulant and antidepressant activities. In vivo antidiabetic activity was performed with pyridine derivative (BVPP) due to in vitro alpha amylase inhibition. In the in vivo antidiabetic study, blood glucose level was significantly reduced after the BVPP treatment in alloxan-induced diabetic rats. BVPP significantly maintained DRSML QAU Abstract Pharmacological Evaluation of Novel Pyridine and Fluorene Derivatives for their Cytotoxicity, Antioxidant, Antimicrobial and Antidiabetic activities: Both In Vivo and In Vitro Analyses xi level of antioxidant enzymes involving catalase, super oxide dismutase and glutathione. Level of oxidative stress markers like lipid peroxidation, hydrogen peroxide and sodium nitrite were also found to be recovered. BVPP showed protective effect on pancreas, heart, kidney and liver against alloxan induced tissue damage. Thus BVPP maintained hypoglycemia after alloxan injection and reduced diabetes related complications. Quantitative structural activity relationship (QSAR) studies can also be done further on these compounds to find out the actual mechanism of action. Keywords: Pyridine derivatives, Fluorene derivatives, In vitro assays, In vivo assays, Antioxidant enzymes, Oxidative stress markers, Histopathological analysis