In silico toxicity profiling of natural product compound libraries from African flora with anti-malarial and anti-HIV properties

Onguéné, Pascal Amoa; Simoben, Conrad V.; Fotso, Ghislain Wabo; Andrae‐Marobela, Kerstin; Khalid, Sami A.; Ngadjui, Bonaventure T.; Mbaze, Luc Meva’a; Ntie‐Kang, Fidele

doi:10.1016/j.compbiolchem.2017.12.002

Cited by 23 publications

(17 citation statements)

References 86 publications

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“…An equivalent value of lethal concentration (LC 50 ), for fish (Fathead Minnows), demonstrating a molecule concentration required to result in 50% of experimentally examined Flathead Minnows to die, LC 50 < 0.5 mM (i.e., log LC 50 < À0.3), causing high acute toxicity. 31 All of the synthesized compounds show no toxicity except 6a, which fell within toxicity range.…”

Section: Predictions Of Pkcsmmentioning

confidence: 81%

“…The maximum tolerated dose of human (Table 9) or maximum recommended tolerated dose (where, MRTD in log mg/kg/day), MRTD, is regarded low when ≤0.477 log mg/kg/day and high >0.477 log mg/kg/day. 31 The results revealed that 4,5a and 5b compounds exhibited high MRTD, while compound 5b showed a slight increase over 0.477 (threshold value) log mg/kg/ day, and rest of compounds showed low MRTD. The oral rat acute toxicity illustrates a compound toxic potency regarding lethal dosage (LD 50 in mol kg À1 ) values.…”

Section: Predictions Of Pkcsmmentioning

confidence: 91%

“…For toxicity of protozoan T. pyriformis, a compound having an expected pIGC 50 value (concentration' negative logarithm needed for 50% growth inhibition in log μg/L) < À0.5 log μg/L is regarded as toxic. 31 All synthesized compounds do not lie within such range, and thus all synthesized compounds are non-toxic for T. pyriformis. An equivalent value of lethal concentration (LC 50 ), for fish (Fathead Minnows), demonstrating a molecule concentration required to result in 50% of experimentally examined Flathead Minnows to die, LC 50 < 0.5 mM (i.e., log LC 50 < À0.3), causing high acute toxicity.…”

Section: Predictions Of Pkcsmmentioning

confidence: 98%

“…Molecular docking is a substantial strategy for structure-based drug design since, at the appropriate binding site, it could provide an idea of new compound binding modes. 30 In this research, binding modes, as well as interactions for active inhibitors having crystal structure S. aureus DNA Gyrase B (PDB ID: 4URO) 31 and N-myristoyltranferase of C. albicans (PDB ID:1IYK), 32 were explored via molecular docking experiments, and they were respectively chosen as target proteins in studies of antibacterial and antifungal docking.…”

Section: Molecular Docking Studymentioning

confidence: 99%

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Novel 6‐hydroxyquinolinone derivatives: Design, synthesis, antimicrobial evaluation, in silico study and toxicity profiling

2021

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Infectious diseases of bacteria and fungi have become a major risk to public health because of antibiotic and antifungal resistance. However, the availability of effective antibacterial and antifungal agents is becoming increasingly limited with growing resistance to existing drugs. In response to that, novel agents are critically needed to overcome such resistance. A new series of 6-hydroxyquinolinone 3, 4, 5a, 5b, 6a and 6b bearing different side chains were synthesized and evaluated as antimicrobials against numbers of bacteria and fungi, using inhibition zone technique. As one of these derivatives, compound 3 was identified as a potent antibacterial and antifungal agent against all tested microorganisms with good minimum inhibitory concentration values comparable to reference drugs. Molecular docking studies were performed on antibacterial and antifungal targets; microbial DNA gyrase B of Staphylococcus aureus (PDB ID: 4URO); N-myristoyltransferase of Candida albicans (PDB ID: 1IYK), respectively, to predict the most probable type of interaction at the active site of the target protein in addition to binding affinities and orientations of docked ligands. Additionally, in silico prediction in terms of detailed physicochemical ADME and toxicity profile relating drug-likeness as well as medicinal chemistry friendliness was performed to all synthesized compounds. The results indicated that a novel 4,6-dihydroxyquinolin-2(1H)-one (3) is likely to be a newly synthesized drug candidate, indicating low toxicity in addition to good in silico absorption. In order to pave the way for more logical production of such compounds, structure-activity and toxicity relationships are also discussed.

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Section: Predictions Of Pkcsmmentioning

confidence: 81%

Section: Predictions Of Pkcsmmentioning

confidence: 91%

Section: Predictions Of Pkcsmmentioning

confidence: 98%

Section: Molecular Docking Studymentioning

confidence: 99%

See 2 more Smart Citations

Novel 6‐hydroxyquinolinone derivatives: Design, synthesis, antimicrobial evaluation, in silico study and toxicity profiling

2021

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“…NPs have been reported to contribute strategically in the drug discovery process either as new drug molecules or the relevant scaffold for the synthesis of novel bioactive molecules. In this study, we are continuing our effort to provide an online free database of NPs from African sources [6b,c–g] . The current collection herein represents the most comprehensive collection of NPs from the Eastern Africa region covering the period 1962 to 2019.…”

Section: Discussionmentioning

confidence: 99%

Pharmacoinformatic Investigation of Medicinal Plants from East Africa

Simoben

Qaseem

Moumbock

et al. 2020

Molecular Informatics

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Medicinal plants have widely been used in the traditional treatment of ailments and have been proven effective. Their contribution still holds an important place in modern drug discovery due to their chemical, and biological diversities. However, the poor documentation of traditional medicine, in developing African countries for instance, can lead to the loss of knowledge related to such practices. In this study, we present the Eastern Africa Natural Products Database (EANPDB) containing the structural and bioactivity information of 1870 unique molecules isolated from about 300 source species from the Eastern African region. This represents the largest collection of natural products (NPs) from this geographical region, covering literature data of the period from 1962 to 2019. The computed physicochemical properties and toxicity profiles of each compound have been included. A comparative analysis of some physico‐chemical properties like molecular weight, H‐bond donor/acceptor, logPo/w, etc. as well scaffold diversity analysis has been carried out with other published NP databases. EANPDB was combined with the previously published Northern African Natural Products Database (NANPDB), to form a merger African Natural Products Database (ANPDB), containing ∼6500 unique molecules isolated from about 1000 source species (freely available at http://african‐compounds.org). As a case study, latrunculins A and B isolated from the sponge Negombata magnifica (Podospongiidae) with previously reported antitumour activities, were identified via substructure searching as molecules to be explored as putative binders of histone deacetylases (HDACs).

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Chemical Characterization, DNA‐Damage Protection, Antiproliferative Activity and in Silico Studies of the Essential Oils from Perralderia coronopifolia Coss.**

Boussaha,

Lassed,

Abdelwahab

et al. 2023

Chemistry & Biodiversity

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In this study, for the first time, we analyzed the chemical composition of essential oils (EOs) steam‐distilled from the flowers and leaves of Perralderia coronopifolia by GC‐FID/MS. The objective was to explore new anticancer and antioxidant bioactive substances and understand their mechanisms of action through the use of plant‐derived natural products. The major chemical components characterizing the EOs were cis‐chrysanthenyl acetate 1, 6‐oxocyclonerolidol 2, cis‐8‐acetoxychrysanthenyl acetate 3, and 6α‐hydroxycyclonerolidol 4, respectively. Furthermore, the EOs inhibited cell proliferation in HeLa (human cervix carcinoma) and PC3 (human prostate cancer) cells and protected plasmid DNA from oxidative damage caused by UV‐photolyzed H2O2. Employing a molecular docking study, we elucidated the main compounds′ inhibition mechanisms. Consequently, the antitumor activity could be related to the inhibitory property of compound 3 against CDC25B phosphatase. The evaluation of ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties and the density functional theory (DFT) calculations of the major compounds, especially compound 3, offer potential insights for designing and developing new cancer drug candidates. In conclusion, our study provides a framework for future research and development in the field by establishing a scientific foundation for the use of Perralderia coronopifolia essential oils as a prospective source of antioxidant and anticancer agents.

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In silico toxicity profiling of natural product compound libraries from African flora with anti-malarial and anti-HIV properties

Cited by 23 publications

References 86 publications

Novel 6‐hydroxyquinolinone derivatives: Design, synthesis, antimicrobial evaluation, in silico study and toxicity profiling

Novel 6‐hydroxyquinolinone derivatives: Design, synthesis, antimicrobial evaluation, in silico study and toxicity profiling

Pharmacoinformatic Investigation of Medicinal Plants from East Africa

Chemical Characterization, DNA‐Damage Protection, Antiproliferative Activity and in Silico Studies of the Essential Oils from Perralderia coronopifolia Coss.**

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