Computational Investigation of the Therapeutic Potential of Detarium senegalense in the Management of Erectile Dysfunction

被引：1

作者：

Ejeje, Jerius Nkwuda ^{[1
,2
]}

Agbebi, Emmanuel Ayodeji ^{[3
,4
]}

Mathenjwa-Goqo, Makhosazana Siduduzile ^{[5
]}

Oje, Obinna Aru ^{[2
]}

Agboinghale, Precious Eseose ^{[1
,6
]}

Ebe, Ikechukwu Theophilus ^{[7
]}

Obafemi, Tajudeen Olabisi ^{[1
]}

Adewole, Ezekiel ^{[8
]}

Omaka, Omaka N. ^{[9
]}

Onikanni, Sunday Amos ^{[1
]}

Ajiboye, Basiru Olaitan ^{[10
]}

Omotuyi, Olaposi Idowu ^{[3
,11
]}

Oyinloye, Babatunji Emmanuel ^{[1
,3
,5
]}

机构：

[1] Afe Babalola Univ, Coll Sci, Phytomed Biochem Toxicol & Biotechnol Res Labs, Dept Biochem, PMB 5454, Ado Ekiti 360001, Nigeria

[2] Alex Ekwueme Fed Univ Ndufu Alike Ikwo, Fac Biol Sci, Dept Biochem, POB 1010, Abakaliki 480101, Nigeria

[3] Afe Babalola Univ, Inst Drug Res & Dev, SE Bogoro Ctr, PMB 5454, Ado Ekiti 360001, Nigeria

[4] Afe Babalola Univ, Coll Pharm, Dept Pharmacognosy & Nat Prod, Ado Ekiti 360001, Nigeria

[5] Univ Zululand, Dept Biochem & Microbiol, Biotechnol & Struct Biol BSB Grp, ZA-3886 Kwa Dlangezwa, South Africa

[6] Univ Ottawa, Fac Sci, Dept Chem & Biomol Sci, Ottawa, ON K1N 6N5, Canada

[7] David Umahi Fed Univ Hlth Sci, Fac Basic Med Sci, Dept Med Biochem, Uburu 491105, Nigeria

[8] Afe Babalola Univ, Dept Chem Sci, Coll Sci, PMB 5454, Ado Ekiti, Ekiti State, Nigeria

[9] Alex Ekwueme Fed Univ, Fac Sci, Dept Phys Geol Geophys, POB 1010, Abakaliki, Ebonyi State, Nigeria

[10] Fed Univ Oye Ekiti, Dept Biochem, Phytomed & Mol Toxicol Res Lab, Oye Ekiti, Nigeria

[11] Afe Babalola Univ, Dept Pharmacol & Toxicol, Coll Pharm, PMB 5454, Ado Ekiti, Nigeria

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2024年 / 25卷 / 22期

关键词：

erectile dysfunction; Detarium senegalense; phosphodiesterase; 5; sildenafil; catechin; epicatechin; QUALITY-OF-LIFE; CORPUS CAVERNOSUM; PENILE ERECTION; GALLIC ACID; DISCOVERY; ARGINASE;

D O I：

10.3390/ijms252212362

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Erectile dysfunction (ED) is a multifactorial social problem affecting men worldwide. While phosphodiesterase type 5 inhibitors (PDE5) like sildenafil are commonly used, they often present side effects, underscoring the need for alternative therapies. Therefore, this study investigated the potential of phytochemicals from Detarium senegalense in the management of ED. A library of phytochemicals from Detarium senegalense was generated, prepared, and interacted with six key enzymes implicated in ED, including PDE5, using the Schr & ouml;dinger Maestro suite. The results identified catechin, epicatechin, and gallic acid as the leading compounds with significant binding affinities for the targeted enzymes. Catechin and epicatechin (-9.877 and -11.408 kcal/mol, respectively) exhibited comparable binding affinities to sildenafil (-11.926 kcal/mol) on PDE5. The MD simulation results also revealed superior stability and ability to maintain interaction with key amino acids at the active site of PDE5 over the entire simulation period for these compounds. These compounds also demonstrated favorable ADMET profiles over sildenafil, including high gastrointestinal absorption and no violation of Lipinski's rule, indicating good bioavailability and drug likeness. These findings suggest that flavonoids from Detarium senegalense, especially catechin and epicatechin, have potential in the management of ED by interacting with multiple targets involved in its pathogenesis.

引用

页数：22

共 66 条

[1] South African plants and male reproductive healthcare: Conception and contraception [J].