title: Synthesis, characterization and biological evaluation of some novel 2,4-thiazolidinediones as potential cytotoxic, antimicrobial and antihyperglycemic agents.
abstract: A series of some novel 2,4-thiazolidinediones (TZDs) (2a-x) have been synthesized and characterized by FTIR, (1)H NMR, (13)C NMR and LC mass spectral analysis. All the synthesized compounds were evaluated for their cytotoxicity, antimicrobial and in vivo antihyperglycemic activities. Among the tested compounds for cytotoxicity using Brine Shrimp Lethality assay, compound 2t ((Z)-5-(4-((E)-3-oxo-3-(thiophen-2-yl)prop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione) exhibited significant inhibitory activity at ED(50) value 4.00±0.25 μg/mL and this level of activity was comparable to that of the reference drug podophyllotoxin with ED(50) value 3.61±0.17 μg/mL. Antimicrobial activity was screened using agar well diffusion assay method against selected Gram-positive, Gram-negative and fungal strains and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. From the results of antimicrobial activity compound 2s ((Z)-5-(4-((E)-3-(3,5-bis(benzyloxy)phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione) was found to be the most active against all the tested strains of microorganisms with MIC value 16 μg/mL. In vivo antihyperglycemic effect of twenty four TZDs (2a-x) at different doses 10, 30 and 50mg/kg b.w (oral) were assessed using percentage reduction of plasma glucose (PG) levels in streptozotocin-induced type II diabetic rat models. From the results, the novel compound 2x ((Z)-5-(4-((E)-3-(9H-fluoren-2-yl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione) exhibited considerably potent blood glucose lowering activity than that of the standard drug rosiglitazone and it could be a remarkable starting point to evaluate structure-activity relationships and to develop new lead molecules with potential cytotoxicity, antimicrobial and antihyperglycemic activities. In addition molecular docking studies were carried out against PPARγ molecular target using Molegro Virtual Docker v 4.0 to accomplish preliminary confirmation of the observed in vivo antihyperglycemic activity.
authors.affiliation: Pharmaceutical Chemistry Division, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530003, Andhra Pradesh, India. vasudevaraoavupati@gmail.com
authors.forename: Vasudeva Rao
authors.initials: VR
authors.lastname: Avupati
authors.forename: Rajendra Prasad
authors.initials: RP
authors.lastname: Yejella
authors.forename: Annapurna
authors.initials: A
authors.lastname: Akula
authors.forename: Girija Sankar
authors.initials: GS
authors.lastname: Guntuku
authors.forename: Bhagya Raju
authors.initials: BR
authors.lastname: Doddi
authors.forename: Venkata Rao
authors.initials: VR
authors.lastname: Vutla
authors.forename: Suvarna Ratna
authors.initials: SR
authors.lastname: Anagani
authors.forename: Lakshmana Santhi
authors.initials: LS
authors.lastname: Adimulam
authors.forename: Aruna Kumar
authors.initials: AK
authors.lastname: Vyricharla
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D001156:Artemia / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D005658:Fungi / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D062105:Molecular Docking Simulation; D009181:Mycoses / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D018675:Toxicity Tests
chemical_list: D000890:Anti-Infective Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; C500090:thiazolidine-2,4-dione