Benzimidazole Molecule Hybrid With Oxadiazole Ring as Antiproliferative Agents: In-Silico Analysis, Synthesis and Biological Evaluation

Rashid, Mohammad

doi:10.4067/s0717-97072021000205164

Cited by 12 publications

(11 citation statements)

References 58 publications

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“…Using Lipinski rule-based ADME criteria, compounds are evaluated as potential to be used as an effective therapeutic option (Lipinski et al, 1997). The SWISS-ADME tool was used to determine a set of ADME-related attributes (Rashid et al, 2021;Mohammed Ali et al, 2022) for each of the selected NPs. The ADME properties of the 74 NPs were analyzed using the SWISS-ADME tool (Daina et al, 2017) to evaluate their druglike suitability and toxicity risk.…”

Section: Computational Pharmacokineticsmentioning

confidence: 99%

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Identification of fungus-growing termite-associated halogenated-PKS maduralactomycin a as a potential inhibitor of MurF protein of multidrug-resistant Acinetobacter baumannii

Shoaib

Shehzadi²,

Asif

et al. 2023

Front. Mol. Biosci.

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Multidrug-resistant Acinetobacter baumannii infections have become a major public health concern globally. Inhibition of its essential MurF protein has been proposed as a potential target for broad-spectrum drugs. This study aimed to evaluate the potential of a novel ecological niche of 374 fungus-growing termite associated Natural Products (NPs). The molecular docking and computational pharmacokinetics screened four compounds, i.e., Termstrin B, Fridamycin A, Maduralactomycin A, and Natalenamide C, as potential compounds that have higher binding affinities and favourable protein-ligand interactions. The compound Maduralactomycin A induced more stability based on its lowest average RMSD value (2.31 Å) and low standard deviation (0.35) supported by the consistent flexibility and β-factor during the protein’s time-dependent motion. While hydrogen bond analysis indicated that Termstrin B has formed the strongest intra-protein interaction, solvent accessibility was in good agreement with Maduralactomycin A compactness. Maduralactomycin A has the strongest binding energy among all the compounds (−348.48 kcal/mol) followed by Termstrin B (−321.19 kcal/mol). Since these findings suggest Maduralactomycin A and Termstrin B as promising candidates for inhibition of MurF protein, the favourable binding energies of Maduralactomycin A make it a more important compound to warrant further investigation. However, experimental validation using animal models and clinical trials is recommended before reaching any final conclusions.

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Section: Computational Pharmacokineticsmentioning

confidence: 99%

“…Toxicology risk alerts are a sign that the depicted structure might be detrimental in relation to the given risk category. Risk alarms, however, are not intended to be a perfectly accurate toxicity prediction (Rashid et al, 2021).…”

Section: Computational Pharmacokineticsmentioning

confidence: 99%

Identification of fungus-growing termite-associated halogenated-PKS maduralactomycin a as a potential inhibitor of MurF protein of multidrug-resistant Acinetobacter baumannii

Shoaib

Shehzadi²,

Asif

et al. 2023

Front. Mol. Biosci.

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“…Furthermore, the red color indication denotes the non-substrate of c, which is shown as (PGP+), but the blue color indication shows that the molecule is actively effluxed by P-glycoprotein, which is shown as (PGP). [ 26 - 28 ]…”

Section: Aterials and M Ethodsmentioning

confidence: 99%

Silver Nanoparticles from Saudi and Syrian Black Cumin Seed Extracts: Green Synthesis, ADME, Toxicity, Comparative Research, and Biological Appraisal

Rashid,

Athar,

Abdelmageed

et al. 2023

Journal of Pharmacy and Bioallied Sciences

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Objective: The current study’s objective is to highlight the value of using plant resources to identify key bioactive molecules and implement green chemistry in research and development to meet market demand. Materials and Methods: The black cumin seeds (Saudi and Syria originated) were utilized to make silver nanoparticles (Ag-NPs), which were subsequently confirmed using a UV spectrophotometer and color analysis of reaction mixtures. The antibacterial activity of Ag-NPs was tested against E. coli, K. pneumoniae, and S. aureus, and antioxidant activity was measured using the DPPH assay. Swiss-ADME, pkCSM, and ProTox-II were also used to assess the pharmacokinetics, oral bioavailability, toxicity, and safety endpoints of molecules. Result: The antibacterial effect of Ag-NPs from Saudi-origin black cumin seeds was observed higher. In comparison to the standard, the Saudi and Syrian Ag-NPs combined displayed synergistic antibacterial effects and were found to be more susceptible to S. aureus. In comparison to the reference, the antioxidant activity of Ag-NPs indicated 60–85% radical scavenging. All molecules passed the Lipinski rule, the filter (Veber, Egan, and Muegge), PAINS, and the Brenk structural alert (zero violations), and the synthetic score was also found to be in the easy limit (1 to 2). The compounds were found to be non-substrate for p-glycoprotein, high GIA% (>90%), non-inhibitor for CYP3A4, CYP2C19, CYP2C9, CYP2D6 (except 5 and 10), Log Po/w (1.71 to 3.26), TPSA 150 2 and MR 155. The compounds likewise had high Caco2 values (log Papp >0.9) with the exception of 4 and 9 (log Papp 0.9), were non-inhibitors of P-gp-I and II and hERG I and II, and showed no AMES toxicity. Except for molecule 11, no organ damage (hepatotoxicity) or endpoint toxicity (mutagenicity, immunotoxicity, carcinogenicity, and cytotoxicity) was identified in ProTox-II. Conclusion: The current study sheds new light on the significance of bioactive molecules found in black cumin seeds, with molecules 3 and 6 identified as potential leads (highest GIA%, no AMES toxicity, oral rat acute and chronic toxicity, lack of renal OCT2 substrate, high total clearance, and lack of organ toxicity) for further research for a variety of medical applications.

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“…In this synthetic route, hydrazines are reacted with α,β-enones in the presence of an acid catalyst to produce the desired pyrazolines (Vahedpour et al, 2021). Furthermore, in silico analysis has proven helpful in predicting a proposed compound's molecular mechanism of action with a receptor (Rashid et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Study of 1-Formyl-2-Pyrazolines as Anticancer Drug Candidates

Suma,

Wahyuningsih

2023

Indonesian J Pharm

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The development of novel anticancer agents is essential in cancer prevention. One versatile group of compounds, known for their significant bioactivity and several of its derivatives that have been clinically approved, is the group of pyrazolines. This study aimed to synthesize 1-formyl-2-pyrazoline derivatives (pyrazolines 1-2) using chalcone 1-2, hydrazine hydrate, and formic acid via cyclo-condensation. The synthesized compounds were characterized using Fourier Transform Infrared (FTIR), Gas Chromatography-Mass Spectrometry (GC-MS), and Nuclear Magnetic Resonance (1H- and 13C-NMR) spectrometers. Pyrazolines 1-2 were found to be drug-like compounds, satisfying Lipinski’s Rule of Five and possessing favourable absorption, distribution, metabolism, and excretion (ADME) properties, including good gastrointestinal absorption, blood-brain barrier permeability, and no interaction with P-glycoprotein. Furthermore, they were inactive against several toxicity endpoints in a normal body condition, such as immunotoxicity, mutagenicity, and cytotoxicity. In vitro cytotoxic evaluation of the pyrazolines 1-2 against HeLa and MCF7 cancer cell lines demonstrated moderate activity, with IC50 values of 25.01 µM and 82.87 µM, respectively. Pyrazolines 1-2 also showed good selectivity with selectivity index (SI) values of 8.92 and 14.45. The molecular docking study on epidermal growth factor receptor tyrosine kinase (EGFR-TK) (PDB ID: 4HJO) revealed that pyrazolines 1-2 had a binding affinity of -7.9 and -8.0 kcal/mol, respectively. The compounds interacted with Lys721 residue through hydrogen bonds and hydrophobic interactions due to the presence of the pyrazoline ring and the formyl group in their structures. These findings suggest that pyrazolines 1-2 scaffold has the potential to be further studied as a lead compound for anticancer drug candidates.

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Benzimidazole Molecule Hybrid With Oxadiazole Ring as Antiproliferative Agents: In-Silico Analysis, Synthesis and Biological Evaluation

Cited by 12 publications

References 58 publications

Identification of fungus-growing termite-associated halogenated-PKS maduralactomycin a as a potential inhibitor of MurF protein of multidrug-resistant Acinetobacter baumannii

Identification of fungus-growing termite-associated halogenated-PKS maduralactomycin a as a potential inhibitor of MurF protein of multidrug-resistant Acinetobacter baumannii

Silver Nanoparticles from Saudi and Syrian Black Cumin Seed Extracts: Green Synthesis, ADME, Toxicity, Comparative Research, and Biological Appraisal

Study of 1-Formyl-2-Pyrazolines as Anticancer Drug Candidates

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