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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]

The date palm , Phoenix dactylifera , is a vital crop in nations in the Middle East and North Africa. The date palm was thought to have outstanding traditional medicinal value because it was abundant in phytochemicals with diverse chemical structures. The date palm's ability to withstand harsh environments could be partly attributed to a class of proteins known as lectins, which are carbohydrate-binding proteins that can bind sugar moieties reversibly and without changing their chemical structures. After scanning the genome of P. dactylifera (GCF 009389715.1), this in silico study discovered 196 possible lectin homologs from 11 different families, some specific to plants. At the same time, others could also be found in other kingdoms of life. Their domain architectures and functional amino acid residues were investigated, and they yielded a 40% true-lectin with known conserved carbohydrate-binding residues. Further, their probable subcellular localization, physiochemical and phylogenetic analyses were also performed. Scanning all putative lectin homologs against the anticancer peptide (ACP) dataset found in the AntiCP2.0 webpage identified 26 genes with protein kinase receptors (Lec-KRs) belonging to 5 lectin families, which are reported to have at least one ACP motif. Our study offers the first account of Phoenix -lectins and their organization that can be used for further structural and functional analysis and investigating their potential as anticancer proteins. [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]