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Background: Plants of the Amaryllidaceae family have been under intense scrutiny for the presence of a couple of alkaloidal secondary metabolites with endued cytotoxic activity, such as pancratistatin (1), 7-deoxypancratistatin (2), narciclasine (3), 7-deoxynarciclasine (4), trans-dihydronarciclasine (5), and 7-deoxy-trans-dihydronarciclasine (6). Nevertheless, preclinical evaluation of these alkaloids has been put on hold because of the limited quantity of materials available from isolation. Aim: To explore the underlying cytotoxic molecular mechanisms of the Amaryllidaceae alkaloids (1-6) and to assess their absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles using chemoinformatic tools. Materials And Methods: AutoDock 4.0 software along with different in silico chemoinformatic tools, namely PharmMapper, Molinspiration, MetaPrint2D, and admetSAR servers, were used to assess the drugability of the Amaryllidaceae alkaloids (1-6). Results: Deoxycytidine kinase (dCK) (PDB: 1P60) was predicted as a potential target with fitting score of 5.574. In silico molecular docking of (1-6) into dCK revealed good interactions, where interesting hydrogen bonds were observed with the amino acid residues-Gly-28 and Ser-35-located in the highly conserved P-loop motif. This motif plays a special role in dCK function. Contrary to (1), in silico pharmacokinetic results have shown good absorption and permeation and thus good oral bioavailability for (2-6). Conclusion: The in silico docking data have proposed that the reported cytotoxic activity of the Amaryllidaceae alkaloids (1-6) could be mediated through dCK inhibition. In addition, the ADMET profile of these alkaloids is promising and thus (1-6) could be candidates for future drug development. [ABSTRACT FROM AUTHOR]

Mycetoma is a distinct flesh eating and destructive neglected tropical disease. It is endemic inmany tropical and subtropical countries. Mycetoma caused by bacterial infections (actinomycetoma) such asStreptomycessomaliensis and Nocardiae or true fungi (eumycetoma) such as M.mycetomatis. To date, treatments fail to cure the infection and the available marketed drugs are expensive and toxic uponprolonged usage. Moreover, no vaccine was prepared yet against mycetoma. The aim of this study is to predict effective epitope-based vaccine against fructose-bisphosphate aldolaseenzymes of M. mycetomatis using immunoinformatic approaches. Materials and Methods: Fructose-bisphosphate aldolase of M.mycetomatis Sequence was retrieved fromNCBI. Different prediction tools were used to analyze the nominee's epitopes in Immune Epitope Databasefor B-cell, T-cell MHC class II & I. Then the proposed peptides were docked using Autodock 4.0 softwareprogram. Results and Conclusions: The proposed and promising peptides KYLQ show a potent bindingaffinity to Bcell,FEYARKHAF with a very strong binding affinity to MHC1 alleles and FFKEHGVPL thatshow a verystrong binding affinity to MHC11and MHC1 alleles. This indicates a strong potential toformulate a newvaccine, especially with the peptide FFKEHGVPL that is likely to be the first proposed epitope-basedvaccine against Fructose-bisphosphate aldolase of M.mycetomatis. This study recommends an in-vivoassessment for the most promising peptides especially FFKEHGVPL. [ABSTRACT FROM AUTHOR]