Synthesis, DNA binding, and cytotoxic evaluation of new analogs of diallyldisulfide, an active principle of garlic.
Diallyldisulfide (DADS), an active principle of garlic (Allium sativum) is known for its antihyperlipidemic properties. However, its use is limited due to its extreme volatility. In the present study, we have synthesized and characterized a series of six new DADS analogs and investigated their interactions with different DNA duplexes. The spectroscopic and circular dichroism (CD) analyses revealed that DADS analogs bind preferentially with GC rich sequences. Thermodynamic parameters suggest that DADS analogs stabilize the calf thymus (CT) DNA and GC rich duplex by favorable enthalpic gains and follow the hierarchy, d(GC)(7)>CT DNA>d(AT)(10). Further, DADS analogs are less toxic and equally effective as the statins. The analogs therefore have a good potential to provide a new therapeutic approach for the treatment of cardiovascular and related diseases.
Rai
Santosh Kumar
SK
Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India.
Sharma
Meenakshi
M
Tiwari
Manisha
M
D000498:Allyl Compounds / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D002478:Cells, Cultured; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D005737:Garlic / Q000737:chemistry*; D022781:Hepatocytes / Q000187:drug effects; D006937:Hypercholesterolemia / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D009691:Nucleic Acid Denaturation; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000737:chemistry* / Q000494:pharmacology*
D000498:Allyl Compounds; D000972:Antineoplastic Agents, Phytogenic; D000960:Hypolipidemic Agents; D013440:Sulfides; C038491:allyl sulfide; D004247:DNA