IDR - IIT Kharagpur

Molecular Interactions of Curcumin Derivatives with Biomacromolecules and Studies on Their Antioxidant Mechanism

Molecular Interactions of Curcumin Derivatives with Biomacromolecules and Studies on Their Antioxidant Mechanism

 

Molecular Interactions Form The Basis Of Molecular Recognition That Associate With Virtually All Cellular Functions In Life Processes Of Biological Systems. Majority Of The Available Drugs Exhibit Their Activity Via Non-Covalent Interactions With Target Biomacromolecules. Recent Years Have Seen Growing Interest In Natural Products And Their Analogues. Curcumin (Cr) Is A Non-Toxic Natural Product Having Diverse Pharmacological Potencies With Established Affinities And Binding Modes. However, The Beneficial Effect Of Cr Is Limited Due To Its Poor Bioavailability. Further The Mechanism Of Action Of Cr Responsible For Its Antioxidant Activity Is A Topic Of Debate. Three Derivatives Of Cr Namely Diacetylcurcumin (Dac), Isoxazolcurcumin (Ioc) And Ethylenediamine Derivative Of Cr (Ced) Possessing Better Potential Over Cr In Some Of Its Activities, Have Been Prepared Following Reported Methods. Human Serum And Bovine Serum Albumins (Hsa And Bsa) Are The Major Soluble Constituents Of The Circulatory System And Are Primary Drug Carrier Proteins. The Functional Role Of Dna In Transcription, Gene Expression And Replication Make It An Extremely Important Potential Target For Drugs With Anticancer, Antibiotic And Antiviral Action. The Interactions Of Dac, Ioc And Ced With Hsa, Bsa And Calf Thymus Dna (Ct-Dna) Have Been Studied Employing Various Biophysical Methods. This Has Been Followed By A Comparative Study On Their Antioxidant Activity To Find Out The Primary Functionality Responsible For The Activity. Dac, Ioc And Ced Bind To Hsa And Bsa At Site 1 Near Trp 214 Of Hsa And Trp 213 Of Bsa In Subdomain Iia With Binding Constants In The Order Of 104 To 105 M-1. Interactions With Proteins Were Observed To Be Entropy Driven. There Is No Significant Conformational Variation In The Secondary Structure Of The Proteins After Binding. The Derivatives Bind To Ct-Dna Preferably In The A-T Rich Region Of The Minor Groove With Binding Constants In The Order Of 104 To 106 M-1. No Conformational Change Of Ct-Dna Was Observed After Binding. The Primary Functionality Responsible For The Antioxidant Activity Of The Derivatives Was Found To Be The Phenolic Oh Groups Though The Side Chain Extending The Conjugation Also Plays A Role.

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