Cholic Acid as a Lead Molecule: A Review

 

Tripathi Kishu¹* and Kumar T. Siva²

¹Institute of Pharmaceutical Sciences & Research Center, Bhagwant University, Ajmer, Rajasthan, India.

²Nandha College of Pharmacy, Tamil Nadu, India

*Corresponding Author E-mail: drkishutripathi@gmail.com

ABSTRACT:

Cholic acid and metal ions both have pharmacological actions like antibacterial, antiviral, antifungal, antimalarial, antitubercular, anticancer, spermicidal, antiallergic etc, therefore, their organometallic complexes were prepared to have synergistic effect. Cholic acid is one of the lead molecule for preparing organometallic complexes and their complexes were found to have more active antibacterial, antiviral, antifungal, antimalarial, antitubercular, anticancer, spermicidal, antiallergic  etc.

 

 

 

INTRODUCTION:

Synonyms: 3,7,12-Trihydroxy-cholan-24-oic acid; 5beta-Cholan-24-oic acid, 3alpha, 7alpha, 12alpha-trihydroxy; Cholan-24-oic acid, 3,7,12-trihydroxy-, (3alpha,5beta,7alpha,12alpha)-;3,7,12-trihydroxycholanic acid; 3α,7α,12α -trihydroxy-5 β -cholan-24-oic acid;3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholanic acid; 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholan-24-ic acid; 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholan-24-oic acid;5-beta-cholanic acid-3-alpha, 7-alpha, 12-alpha-triol;7-alpha,8-alpha,12-alpha-trihydroxy-5-beta-cholan-24-oic acid; cholalic acid;cholalin;cholan-24-oic acid;cholan-24-oic acid, 3,7,12-trihydroxy-, (3,5,7,12)-;cholic acid;ca;12α-Trihydroxy-5β-cholan-24-oic acid.; 3α,7α,12α-Trihydroxy-5α-cholanic acid; Cholic acid; Cyclosphorine

 

This is a well known fact that all the surfactants whether anionic, cationic or non-ionic; whether they are hydrophilic, lipophilic or amphiphilic possesses antimicrobial properties in suitable doses. However, amphiphilic surfactants are of vital importance because of suitable Hydrophilic- Lipophilic Balance (HLB).Certain steroidal compounds pharmacophoric groups like cholic acid or its derivatives, estrogens etc which may be hydrophilic, lipophilic or with suitable balance of these can reduce surface tension which may induce antimicrobial activity.

 

Cholic acid, a main bile acid, is a biosurfactant involved in the digestion of dietary lipids .It is commercially available at low cost. Futhermore, it has an unusual molecular structure with some special characteristics, such as the facial amphiphilicity. The carboxylic acid and three hydroxylic groups can act as synthesis handles. For these reasons cholic acid is a suitable building block for new functional molecules.

 

Because of the differences in steric hindrance each hydroxyl group can be derivatized individually. Therefore, cholic acid can be used as a scaffold for combinatorial chemistry and asymmetric synthesis. Not only the co-directed hydroxyl groups are useful for these purposes, but also the side chain with a carboxylic group is important since it provides attachment point to the solid phase. The rigid steroid unit of cholic acid has a curvature, which facilitate the construction of cyclic compounds, so called cholaphanes. These compounds are widely used as receptors for small molecules. Also many other types of receptors were built from cholic acid in which usually two or more molecules are linked together to form a tweezer -type of receptor.

 

Cholic acid having nitrogen containing groups attached to the hydroxylic groups, which permeabilize the outer bacterial membrane. A short alkyl chain at the place of carboxylic group promotes transport through the membrane. Therefore, exhibit antimicrobial activity. Because of their interaction with bilayers, cholic acid derived facial amphiphiles can also be used as membrane fusogens . Other medical applications of cholic acid derivatives are as drug-delivery agents, as transfection agents and as X-ray contrast agents. In all these cases cholic acid facilitates transport of more polar molecules across the membrane bilayer by sheilding them from the apolar interior. Cholic acid derivatives have been used for chiral separations, e. g as stationary phase for HPLC and in inclusion chemistry.

 

Cholic acid, a natural biodetergent has been reported to exhibited antibacterial^11-14, antiviral⁵, antifungal ⁴, antimalarial¹⁰, antitubercular¹⁰, anticancer⁹, spermicidal^{2, 3}, antiallergic ^6,7,8 etc. Since cholic acid is a suitable building block for new molecules or in other words, it is a lead compound for the development of various compounds, therefore, it is thought worthwhile to select it for the research work.

 

The antimicrobial activity of metal chelates was found to be in the order¹:

 

Cd ^II>Ni ^II >Mn ^II >Cu ^II >Zn ^II >Co ^II >Fe ^II

 

This is rather alarming and hence it is time to consider novel approaches for the treatment of infection besides the conventional therapy.

 

Since complexes of cholic acid with platinum and gold only having anticancer activity were reported in the literatures but other metals also exhibited the antimicrobial activity, therefore, it is thought worthwhile to prepare the organometallic complexes of cholic acid which will lead to the development of multifunctional drugs to exhibit synergistic activity.

 

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Received on 08.03.2011        Modified on 02.04.2011

Accepted on 10.04.2011        © AJRC All right reserved