Synthesis, characterization, drug-likeness properties and determination of the in vitro antioxidant and cytotoxic activities of new 1,3,4-oxadiazole derivatives

Nazarbahjat, Nafal; Ariffin, Azhar; Abdullah, Zanariah; Abdulla, Mahmood Ameen; Shia, John Kwong Siew; Leong, Kok Hoong

doi:10.1007/s00044-016-1660-5

Cited by 6 publications

(4 citation statements)

References 42 publications

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“…We investigated the ADMET (Ro3) of the top five hits in this context, and the findings are reported in Supplementary Table S2 . Overall, the five hits demonstrated adequate drug-related characteristics and skills [ 38 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

Unravelling driver genes as potential therapeutic targets in ovarian cancer via integrated bioinformatics approach

Beg,

Parveen,

Fouad

et al. 2024

J Ovarian Res

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Target-driven cancer therapy is a notable advancement in precision oncology that has been accompanied by substantial medical accomplishments. Ovarian cancer is a highly frequent neoplasm in women and exhibits significant genomic and clinical heterogeneity. In a previous publication, we presented an extensive bioinformatics study aimed at identifying specific biomarkers associated with ovarian cancer. The findings of the network analysis indicate the presence of a cluster of nine dysregulated hub genes that exhibited significance in the underlying biological processes and contributed to the initiation of ovarian cancer. Here in this research article, we are proceeding our previous research by taking all hub genes into consideration for further analysis. GEPIA2 was used to identify patterns in the expression of critical genes. The KM plotter analysis indicated that the out of all genes 5 genes are statistically significant. The cBioPortal platform was further used to investigate the frequency of genetic mutations across the board and how they affected the survival of the patients. Maximum mutation was reported by ELAVL2. In order to discover viable therapeutic candidates after competitive inhibition of ELAVL2 with small molecular drug complex, high throughput screening and docking studies were used. Five compounds were identified. Overall, our results suggest that the ELAV-like protein 2-ZINC03830554 complex was relatively stable during the molecular dynamic simulation. The five compounds that have been found can also be further examined as potential therapeutic possibilities. The combined findings suggest that ELAVL2, together with their genetic changes, can be investigated in therapeutic interventions for precision oncology, leveraging early diagnostics and target-driven therapy.

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Section: Resultsmentioning

confidence: 99%

Unravelling driver genes as potential therapeutic targets in ovarian cancer via integrated bioinformatics approach

Beg,

Parveen,

Fouad

et al. 2024

J Ovarian Res

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“…The QikProp module output data generated for the compounds indicated that the blood–brain barrier (BBB) was in the range of −0.38 to −4.28 with QPlogPo/w between −0.55 and 5.73, QPlogKhsa between −0.63 and 1.14, SASA between 714.08 and 1,083.70, and log K p value ranging from −2.41 to −10.90. Overall, the four hits showed fair enough properties and ability needed for a drug to possess ( Lee et al, 2003 ; Lipinski, 2016 ; Nazarbahjat et al, 2016 ; Cordeiro and Kachroo, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Identification of PARP12 Inhibitors By Virtual Screening and Molecular Dynamics Simulations

et al. 2022

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Poly [adenosine diphosphate (ADP)-ribose] polymerases (PARPs) are members of a family of 17 enzymes that performs several fundamental cellular processes. Aberrant activity (mutation) in PARP12 has been linked to various diseases including inflammation, cardiovascular disease, and cancer. Herein, a large library of compounds (ZINC-FDA database) has been screened virtually to identify potential PARP12 inhibitor(s). The best compounds were selected on the basis of binding affinity scores and poses. Molecular dynamics (MD) simulation and binding free energy calculation (MMGBSA) were carried out to delineate the stability and dynamics of the resulting complexes. To this end, root means deviations, relative fluctuation, atomic gyration, compactness, covariance, residue-residue contact map, and free energy landscapes were studied. These studies have revealed that compounds ZINC03830332, ZINC03830554, and ZINC03831186 are promising agents against mutated PARP12.

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“…Human intestinal absorption (HIA), permeation through the blood–brain barrier (BBB), and drug assessment for substrates of p-glycoproteins (p-gp) are crucial pharmacokinetic properties. They can be used in the early discovery process to determine the extent of intestinal absorption of a bioactive compound in humans [ 33 , 34 , 35 , 36 ]. The result presented in Figure 9 reveal that more than 77% of the AMNPs (compounds found within the white and yellow regions) were likely to be passively absorbed.…”

Section: Resultsmentioning

confidence: 99%

Cheminformatic Profiling and Hit Prioritization of Natural Products with Activities against Methicillin-Resistant Staphylococcus aureus (MRSA)

2021

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Several natural products (NPs) have displayed varying in vitro activities against methicillin-resistant Staphylococcus aureus (MRSA). However, few of these compounds have not been developed into potential antimicrobial drug candidates. This may be due to the high cost and tedious and time-consuming process of conducting the necessary preclinical tests on these compounds. In this study, cheminformatic profiling was performed on 111 anti-MRSA NPs (AMNPs), using a few orally administered conventional drugs for MRSA (CDs) as reference, to identify compounds with prospects to become drug candidates. This was followed by prioritizing these hits and identifying the liabilities among the AMNPs for possible optimization. Cheminformatic profiling revealed that most of the AMNPs were within the required drug-like region of the investigated properties. For example, more than 76% of the AMNPs showed compliance with the Lipinski, Veber, and Egan predictive rules for oral absorption and permeability. About 34% of the AMNPs showed the prospect to penetrate the blood–brain barrier (BBB), an advantage over the CDs, which are generally non-permeant of BBB. The analysis of toxicity revealed that 59% of the AMNPs might have negligible or no toxicity risks. Structure–activity relationship (SAR) analysis revealed chemical groups that may be determinants of the reported bioactivity of the compounds. A hit prioritization strategy using a novel “desirability scoring function” was able to identify AMNPs with the desired drug-likeness. Hit optimization strategies implemented on AMNPs with poor desirability scores led to the design of two compounds with improved desirability scores.

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Synthesis, characterization, drug-likeness properties and determination of the in vitro antioxidant and cytotoxic activities of new 1,3,4-oxadiazole derivatives

Cited by 6 publications

References 42 publications

Unravelling driver genes as potential therapeutic targets in ovarian cancer via integrated bioinformatics approach

Unravelling driver genes as potential therapeutic targets in ovarian cancer via integrated bioinformatics approach

Identification of PARP12 Inhibitors By Virtual Screening and Molecular Dynamics Simulations

Cheminformatic Profiling and Hit Prioritization of Natural Products with Activities against Methicillin-Resistant Staphylococcus aureus (MRSA)

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