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A receptor peroxisome proliferator activated receptor-gamma was targeted by series of new fatty acid chemical entities (M1-M22) which was designed, synthesized and characterized by spectral analysis. Metabolites molecular properties were calculated using Lipinski's rule of five using molinspiration online software. Docking studies were done on co-crystallized protein structure of PPAR γ, PDB-1FM9 showing M15, M17 and M8 to be best located in the active sites with scores -10.43, -10.21 and -10.00 respectively. The free binding energy estimation was done using model of Maestro 9.0 (Schrodinger) and lies between -80.15 to -61.26 kcal/mol which is significant as compared to that of standard (-48.58 Kcal/mol). Nine best docked derivatives were evaluated in-vivo for oral glucose tolerance and antihyperglycemic activity by streptozotocin induced diabetes model and M15 exhibited most promising antidiabetic activity more than the standard glibenclamide. The promising results encourage future investigation on fatty acids for development of active compounds. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Novel series of Schiff base derivatives of octadec-9-enoic acid have been synthesized. • Molecular properties of metabolites were calculated using Lipinski's rule of five. • Molecular docking study was done on active site of co-crystallized structure of PPAR-γ using PDB ID1FM9. • Compounds S21, S10 and S7 exhibited most promising anti-diabetic activity. • Synthesized fatty acid derivatives can be further investigated to develop more active anti-diabetic drugs. Abstract A new series of octadec-9-enoic acid schiff base entities (S1-S30) were designed and synthesized targeting peroxisome proliferator activated receptor-gamma for agonist action. Molinspiration software (online) was used to estimate drug like molecular properties of the metabolites. Docking disquisition on co-crystallized protein of PPAR-γ (PDB ID 1FM9) was carried out which showed S21 , S10 and S7 as best situated in the vital sites of receptor having docking scores −9.19, −8.68 and −8.64 respectively. Free binding energy measured using model of Maestro 9.0 and was in range of from −40.01 and −80.54 kcal/mol, significant when compared with pioglitazone (−51.58 Kcal/mol). Seven best docked derivatives were assessed for in-vivo oral glucose tolerance on normal rats and anti-hyperglycaemic activity by streptozotocin induced diabetes model. S21 unveiled to be the best measured analogue among all the synthesized entities. Encouraging outcomes motivates fatty acids for further development of more effective and safer compounds. [ABSTRACT FROM AUTHOR]

A small library of new benzothiazole clubbed oxadiazole-Mannich bases ( M-1 to M-22 ) were synthesized and characterized by IR, NMR, Mass and Elemental analysis results. Molecular docking studies were done to assess the binding mode and interactions of synthesized hits at binding site of receptor Peroxisome proliferator-activated receptor, PPAR-γ or PPARG (PDB 1FM9 ). Among the synthesized compounds, nine compounds were selected on the basis of docking score and evaluated for their in vivo anti-diabetic activity using Oral Glucose Tolerance Test (OGTT) in normal rats followed by Streptozotocin (STZ) - induced diabetes. Results indicated that compound M-14 (161.39 ± 4.38) showed the highest reduction of blood glucose level comparable to that of the standard drug glibenclamide (140.29 ± 1.24) in STZ model. Other compounds exhibited moderate to good anti hyperglycaemic activity. ADME studies was done using Molinspiration online software, revealed that all compounds (except M-11) are likely to be orally active as they obeyed Lipinski’s rule of five. [ABSTRACT FROM AUTHOR]