Your browser doesn't support javascript.
loading
Exploring the Molecular Mechanisms of 17ß-HSD5-induced Carcinogenicity of Catha edulis via Molecular Modeling Approach.
Saeed, Maria; Ashraf, Sajda; Alsanosi, Rashad; Alhazmi, Hassan A; AlBratty, Mohammed; Najmi, Asim; Khalid, Asaad; Ul-Haq, Zaheer.
Afiliação
  • Saeed M; Dr. Pajwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi-75270, Pakistan.
  • Ashraf S; Dr. Pajwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi-75270, Pakistan.
  • Alsanosi R; Substance Abuse and Toxicology Research Centre, Jazan University, P.O. Box 114, Postal Code: 45142, Jazan, Saudi Arabia.
  • Alhazmi HA; Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, P.O. Box 114, Jazan 45142, Saudi Arabia.
  • AlBratty M; Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, P.O. Box 114, Jazan 45142, Saudi Arabia.
  • Najmi A; Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, P.O. Box 114, Jazan 45142, Saudi Arabia.
  • Khalid A; Substance Abuse and Toxicology Research Centre, Jazan University, P.O. Box 114, Postal Code: 45142, Jazan, Saudi Arabia.
  • Ul-Haq Z; Dr. Pajwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi-75270, Pakistan.
Med Chem ; 17(4): 418-428, 2021.
Article em En | MEDLINE | ID: mdl-33019937
ABSTRACT

BACKGROUND:

The tradition of khat chewing has been deep-rooted in the African and Arabian Peninsula for centuries. Due to its amphetamine-like psycho-stimulant or euphoric effect, khat has been used by millions in Somalia, Ethiopia, Saudi Arabia and Yemen. The long-term use of khat can induce many major health outcomes, which may be serious and irreversible.

OBJECTIVE:

Prolonged use of khat constituents has been associated with different types of cancers such as prostatic, breast and ovarian cancer. However, it has been very difficult to identify the molecular targets involved in khat carcinogenesis that interact with the Khat constituents by in vitro/in vivo experimental tools.

METHODS:

In silico tools were used to predict potential targets involved in the carcinogenesis of khat. Pass on-line prediction server was used for the prediction of a potential molecular target for khat constituents. Molecular Dynamics simulation and MM-GBSA calculation of the predicted target were carried out.

RESULTS:

Molecular Dynamics simulation and MM-GBSA calculation revealed that among khat constituents, ß-sitosterol showed a high binding affinity towards 17ß-HSD5. On the other hand, this study highlights for the first time some new interactions, which were observed in the case of cathine, cathinone and nerol during the simulation.

CONCLUSION:

In silico molecular dynamic simulation tools were used for the first time to investigate the molecular mechanism of widely used leaves of psychoactive khat (Catha edulis) constituent. The present study provides deep insight to understand the effect of khat constituents involved in the impairment of the reproductive system and its binding to 17ß-HSD5. ADMET profiling also suggested that few khat constituents do not fulfill the requirements of the Lipinski rule of five i.e. poor absorption and blood-brain barrier impermeability.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinógenos / Catha / Membro C3 da Família 1 de alfa-Ceto Redutase Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinógenos / Catha / Membro C3 da Família 1 de alfa-Ceto Redutase Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article