The use of the substrate-heme complex approach in the design, synthesis, biochemical evaluation, and rationalization of the inhibitory activity of a range of azole compounds against cholesterol side chain cleavage enzyme.
Here, we report the synthesis and biochemical evaluation of a number of compounds as potent inhibitors of cytochrome P450 enzymes, such as aromatase (AR), but not cholesterol side chain cleavage (CSCC). This is a crucial enzyme in the steroidal cascade and its inhibition results in major side-effects, as a result, the ability of compounds to specifically inhibit enzymes such as AR but not CSCC would be an important factor in the drug design process.
Ahmed
S
S
School of Chemical and Pharmaceutical Sciences, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey, KT1 2EE, United Kingdom. S.AHMED@KINGSTON.AC.UK
D000818:Animals; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors; D001393:Azoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002417:Cattle; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006418:Heme / Q000378:metabolism*; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology; D015394:Molecular Structure; D011485:Protein Binding
D047072:Aromatase Inhibitors; D001393:Azoles; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007527:Isoenzymes; D006418:Heme; D001141:Aromatase; D002786:Cholesterol Side-Chain Cleavage Enzyme