Synthesis and biological evaluation of novel N-arylidenequinoline-3-carbohydrazides as potent β-glucuronidase inhibitors.
Thirty N-arylidenequinoline-3-carbohydrazides (1-30) have been synthesized and evaluated against β-glucuronidase inhibitory potential. Twenty four analogs showed outstanding β-glucuronidase activity having IC50 values ranging between 2.11±0.05 and 46.14±0.95 than standard d-saccharic acid 1,4 lactone (IC50=48.4±1.25μM). Six analogs showed good β-glucuronidase activity having IC50 values ranging between 49.38±0.90 and 80.10±1.80. Structure activity relationship and the interaction of the active compounds and enzyme active site with the help of docking studies were established. Our study identifies novel series of potent β-glucuronidase inhibitors for further investigation.
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia. Electronic address: taha_hej@yahoo.com.
Muhammad
M
Taha
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Pharmacy, Universiti Tecknologi MARA, Puncak Alam, 42300 Selangor, Malaysia. Electronic address: sadiasultan301@yahoo.com.
Sadia
S
Sultan
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Pharmacy, Universiti Tecknologi MARA, Puncak Alam, 42300 Selangor, Malaysia.
Herizal Ali
HA
Nuzar
Department of Chemistry, Hazara University, Mansehra 21300, Pakistan.
Fazal
F
Rahim
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia.
Syahrul
S
Imran
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia.
Nor Hadiani
NH
Ismail
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Pharmacy, Universiti Tecknologi MARA, Puncak Alam, 42300 Selangor, Malaysia.
Humera
H
Naz
Department of Chemistry, Hazara University, Mansehra 21300, Pakistan.
Hayat
H
Ullah
D006023:Glycoproteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship
D006023:Glycoproteins; D006834:Hydrazines; C011473:beta-glucuronidase inhibitor; C019289:carbohydrazide
Molecular docking; N-Arylidenequinoline-3-carbohydrazides; Structure activity relationship; Synthesis; β-Glucuronidase inhibitory potential