Title : Screening of phytochemicals compounds from chasmanthera dependens and carissa edulis as potential inhibitors of carbonic anhydrases CA II (3HS4) receptor using a target-based drug design
Abstract:
Epilepsy is one of the troublesome and unresolved diseases that affect over sixty-five (65) million people around the globe, it occurs due to a brain disorder and despite the availability of commercial anti-epileptic drugs, the war against this unmet condition is yet to be resolved and calls for urgent attention because most epilepsy patients are resistant to available anti-epileptic medications thus the need for affordable novel therapy against epilepsy is a necessity. Numerous phytochemicals have been reported for their potency, efficacy and safety as therapeutic agents against many diseases.
Ninety-nine (99) isolated phytochemicals from Chasmanthera dependens and Carissa edulis were identified from this study and investigated against carbonic anhydrase (ii) drug target. The absorption, distribution, metabolism, excretion and toxicity (ADMET) of the isolated compounds were verified using admet SAR-2 web server. The oral bioavailability, drug-likeness and lead-likeness properties of the selected leads were analyzed using Swiss ADME. PASS web server was used to predict the biological activities of selected leads while other important physicochemical properties and interactions of the selected leads with the active site of the target after successful molecular docking simulation with the pyrx virtual screening tool were also examined.
Seven lead compounds were identified from this study they include; C49- alpha-carissanol (-7.6 kcal/mol), C13- Catechin (-7.4 kcal/mol), C45- Salicin (-7.4 kcal/mol), C6- Bisnorargemonine (-7.3 kcal/mol), C36- Pallidine (-7.1 kcal/mol), S4- Lacosamide (-7.1 kcal/mol), and S7- Acetazolamide (-6.4 kcal/mol) for CA II (3HS4 receptor). These lead compounds are probable inhibitors of this drug target due to the observed good binding affinities and favourable interactions with the active site of the drug target, excellent ADMET profiles, PASS Properties, drug-likeness, lead-likeness and oral bioavailability properties. The identified leads have better binding energies as compared to the binding energies of the two standards. Thus, seven identified lead compounds can be developed further towards the development of new anti-epileptic medications.
Keywords: Drug-likeness, phytochemicals, Carbonic anhydrases, Metalloeazymes, Active site, ADMET
