Virtualizing the p-ANAPL Library: A Step towards Drug Discovery from African Medicinal Plants

Abstract

BackgroundNatural products play a key role in drug discovery programs, both serving as drugs and as templates for the synthesis of drugs, even though the quantities and availabilities of samples for screening are often limitted.Experimental approachA current collection of physical samples of > 500 compound derived from African medicinal plants aimed at screening for drug discovery has been made by donations from several researchers from across the continent to be directly available for drug discovery programs. A virtual library of 3D structures of compounds has been generated and Lipinski’s “Rule of Five” has been used to evaluate likely oral availability of the samples.ResultsA majority of the compound samples are made of flavonoids and about two thirds (2/3) are compliant to the “Rule of Five”. The pharmacological profiles of thirty six (36) selected compounds in the collection have been discussed.Conclusions and implicationsThe p-ANAPL library is the largest physical collection of natural products derived from African medicinal plants directly available for screening purposes. The virtual library is also available and could be employed in virtual screening campaigns.

Application of Computer Modeling to Drug Discovery: Case Study of PRK1 Kinase Inhibitors as Potential Drugs in Prostate Cancer Treatment

“…A summary of small molecule libraries utilizable in virtual screening experiments has been provided in Table 1. Known cancer drugs have been included in several databases, including ChEBI [43], ChEMBL [44], DrugBank [46], EpiDBase [48], NANPDB [51], NCI-DIS, NCI-DTP, and NCI-FDA [52], along with SANCDB [54], SuperDrug [55], p-ANAPL [58], PubChem [59], and ZINC15 [60]. However, those with tested and proven in vitro activities against known cancer cell lines and/or with known in vivo activities only include CancerDR [41], OAA [53], and SYFPEITHI [56], along with the NP libraries: AfroCancer [40], CancerHSP [42], CHMIS-C [43], InPACdb [49], MAPS [50], NPACT [7], and TIPdb [57].…”

The chemistry and bioactivity of Southern African flora I: a bioactivity versus ethnobotanical survey of alkaloid and terpenoid classes

“…45 Waffo et al identied the furoquinoline alkaloids; evoxine (10) and 7-(g,g-dimethylallyloxy)g-fagarine (11), among other compounds including the acridone alkaloids; tegerrardin A (12), tegerrardin B (13), arborinine (14), evoxanthine (15), 1,3-dimethoxy-N-methylacridone (16) and tecleanone (17) from the stem bark of this plant and tested their antiplasmodial activity against the CQS D10 strain of P. falciparum. 45 Waffo et al identied the furoquinoline alkaloids; evoxine (10) and 7-(g,g-dimethylallyloxy)g-fagarine (11), among other compounds including the acridone alkaloids; tegerrardin A (12), tegerrardin B (13), arborinine (14), evoxanthine (15), 1,3-dimethoxy-N-methylacridone (16) and tecleanone (17) from the stem bark of this plant and tested their antiplasmodial activity against the CQS D10 strain of P. falciparum.…”

“…Previous review papers have been focused on the bioactivity versus ethnobotanical survey of medicinal plants from Central, Western and Northern Africa has been done and published by this research group, 3,7,12,13 including the development of natural product databases (CamMedNP, ConMedNP, AfroDb, p-ANAPL) [14][15][16][17] and the pharmacokinetic proling of natural products from African ora, [17][18][19] with the view of drug discovery. Previous review papers have been focused on the bioactivity versus ethnobotanical survey of medicinal plants from Central, Western and Northern Africa has been done and published by this research group, 3,7,12,13 including the development of natural product databases (CamMedNP, ConMedNP, AfroDb, p-ANAPL) [14][15][16][17] and the pharmacokinetic proling of natural products from African ora, [17][18][19] with the view of drug discovery.…”

Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and <em>in Vitro </em>Testing

“…Since the p-ANAPL library consists of compounds with a broad range of already reported activities, e.g. antibacterial, antiviral, anticancer, anti-inflammatory and properties [10], this collection represents a good starting point to search for novel inhibitors or modulators of sirtuins. Sirtuins share a highly conserved catalytic core composed of two subdomains; a large NAD + binding domain (Rossmann fold) and a smaller domain generated by two insertions in the NAD + binding domain, together with a helical module and a zinc-binding module [29,30].…”