Synthesis of new N-acryl-1-amino-2-phenylethanol and N-acyl-1-amino-3-aryloxypropanols and evaluation of their antihyperlipidemic, LDL-oxidation and antioxidant activity.
As a part of our drug discovery program, we identified an alkaloidal amide i.e. Aegeline (V) isolated from the leaves of Aegle marmelos as a dual acting agent (antihyperlipidemic and antihyperglycemic). In continuation of this program, we synthesized new N-acyl-1-amino-2-alcohols (N-acrylated-1-amino-2-phenylethanol and N-acylated-1-amino-3-aryloxypropanols) via Ritter reaction and screened for their in-vivo antihyperlipdemic activity in Triton induced hyperlipidemia model, LDL-oxidation and antioxidant activity. Compounds 3, 11 and 13 showed good antihyperlipidemic activity, LDL-oxidation as well as antioxidant activity and comparable activity with marketed antidyslipidemic drug.
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226 031, U.P., India.
Satinath
S
Sarkar
Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow 226 031, U.P., India.
Ravi
R
Sonkar
Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow 226 031, U.P., India.
Gitika
G
Bhatia
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226 031, U.P., India. Electronic address: tnarender@rediffmail.com.
Narender
N
Tadigoppula
D000433:1-Propanol / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D045471:Aegle / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D060326:Chemistry Techniques, Synthetic; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008071:Lipoprotein Lipase / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves / Q000737:chemistry; D011092:Polyethylene Glycols / Q000009:adverse effects; D051381:Rats
D000975:Antioxidants; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D011092:Polyethylene Glycols; D000433:1-Propanol; D008071:Lipoprotein Lipase; D010626:Phenylethyl Alcohol
Aegeline; Antihyperlipidemic activity; LDL-oxidation anti-oxidant activity; N-Acyl-1-amino-2-alcohols; Triton model