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Fulltext Dual activity of indolin-2-ones containing an arylidene motif: DNA and BSA interaction

Bukhari SNA, Alsahli TG, Ejaz H, Ahmed N, Ahmad W, Elsherif MA, et al.

RSC Adv, 2023 Sep 18;13(40):28139-28147.
PMID: 37753394 DOI: 10.1039/d3ra04997c

Applying a multistep approach, novel indolin-2-ones (IND) that possess an arylidene motif have been synthesized. Eight compounds were chosen for different biological tests (antimicrobial and cytotoxicity). IND containing 2-thienyl (4h) fragment have been found to exhibit good antimicrobial activity against B. cereus. Molecules that have 3-aminophenyl (4d) or 2-pyridyl (4g) groups have shown the best antifungal activities against all tested fungi. These compounds have also been noticed as promising pharmaceuticals against MCF-7 cancer cell lines. Experimental outcomes from the investigation of the interaction of 4d with DNA implied its moderate binding to DNA (KSV = 1.35 × 104 and 3.05 × 104 M-1 for EB and Hoechst binder, respectively). However, considerably stronger binding of 4d to BSA has been evidenced (Ka = 6.1 × 106 M-1). In summary, IND that contains m-aminobenzylidene fragment (4d) exhibits a good dual biological activity making it a promising candidate for further investigation in the drug discovery sector.
Structural vaccinology, molecular simulation and immune simulation approaches to design multi-epitopes vaccine against John Cunningham virus

Suleman M, Khan TA, Ejaz H, Maroof S, Alshammari A, Albekairi NA, et al.

Microb Pathog, 2024 Apr;189:106572.
PMID: 38354987 DOI: 10.1016/j.micpath.2024.106572

The JCV (John Cunningham Virus) is known to cause progressive multifocal leukoencephalopathy, a condition that results in the formation of tumors. Symptoms of this condition such as sensory defects, cognitive dysfunction, muscle weakness, homonosapobia, difficulties with coordination, and aphasia. To date, there is no specific and effective treatment to completely cure or prevent John Cunningham polyomavirus infections. Since the best way to control the disease is vaccination. In this study, the immunoinformatic tools were used to predict the high immunogenic and non-allergenic B cells, helper T cells (HTL), and cytotoxic T cells (CTL) epitopes from capsid, major capsid, and T antigen proteins of JC virus to design the highly efficient subunit vaccines. The specific immunogenic linkers were used to link together the predicted epitopes and subjected to 3D modeling by using the Robetta server. MD simulation was used to confirm that the newly constructed vaccines are stable and properly fold. Additionally, the molecular docking approach revealed that the vaccines have a strong binding affinity with human TLR-7. The codon adaptation index (CAI) and GC content values verified that the constructed vaccines would be highly expressed in E. coli pET28a (+) plasmid. The immune simulation analysis indicated that the human immune system would have a strong response to the vaccines, with a high titer of IgM and IgG antibodies being produced. In conclusion, this study will provide a pre-clinical concept to construct an effective, highly antigenic, non-allergenic, and thermostable vaccine to combat the infection of the John Cunningham virus.
A Review of In Silico and In Vitro Approaches in the Fight Against Carbapenem-Resistant Enterobacterales

Absar M, Zaidah AR, Mahmood A, Ahmad S, Ejaz H, Ahmed N, et al.

J Clin Lab Anal, 2025 Apr 09.
PMID: 40205812 DOI: 10.1002/jcla.70018

OBJECTIVES: The rise in carbapenem-resistant Enterobacterales (CRE) has reinforced the global quest for developing effective therapeutics. Traditional drug discovery approaches have been inadequate in overcoming this challenge due to their resource and time constraints.
METHODS: English literature was searched by structured queries related to our review between January 1, 2020, and December 31, 2024.
RESULTS: The key resistance mechanisms in CRE, such as enzymatic hydrolysis, decreased permeability, and efflux pump overexpression, have been examined in this review. Computational technologies have become pivotal in discovering novel antimicrobial agents with improved accuracy and efficiency. Besides this, the review highlights the advances in structure- and ligand-based drug discovery approaches for identifying potential drugs against CRE. Recent studies demonstrating the use of such in silico techniques to develop targeted drugs against CRE have also been explored. Moreover, this review also underscores the significance of integrating both in silico and in vitro techniques to counter resistance in Enterobacterales, supported by the latest studies. However, these promising computational technologies have a few major drawbacks, such as a lack of standardized parameterization, potentially false positives, and the complexity of effective clinical translations. The drug regulatory barriers also restrict the progress of new antimicrobials for market approval.
CONCLUSION: The use of computational technologies for antimicrobial inhibitor discovery is gaining popularity, and it can be expedited by refining computational techniques and integrating them with reliable in vitro validation. The use of innovative hybrid in silico and in vitro technologies is the need of the hour to tackle CRE and mitigate the global threat of antimicrobial resistance.

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