In-silico molecular design of heterocyclic benzimidazole scaffolds as prospective anticancer agents

Tahlan, Sumit; Kumar, Sanjiv; Ramasamy, Kalavathy; Lim, Siong Meng; Mani, Vasudevan

doi:10.1186/s13065-019-0608-5

Cited by 48 publications

(40 citation statements)

References 38 publications

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“…Two analogous catalytic sites are localized between each of the dimer pairs and are correlated by a noncrystallographic two-fold axis. e virtual docking was performed for the most active compounds (4a and 5a) in order to rationalize the activity of these compounds against malaria [56].…”

Section: Antiprotozoal Activitymentioning

confidence: 99%

New Benzoxazole Derivatives as Antiprotozoal Agents: In Silico Studies, Synthesis, and Biological Evaluation

Abdelgawad

Al-Sanea

Zaki

et al. 2021

Journal of Chemistry

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Background. Benzoxazole derivatives have different biological activities. In pursuit of designing novel chemical entities with antiprotozoal and antimicrobial activities, benzoxazolyl aniline was utilized as a privileged scaffold of a series of (3-benzoxazole-2-yl) phenylamine derivatives, 3-benzoxazoloyl acetamide, and butyramide derivatives. Methods. These novel analogs were synthesized in straightforward simple chemistry without any quantitative chromatographic separations in reasonable yields. The biological evaluation of all target compounds as potential antimalarial, antileishmanial, antitrypanosomal, and antimicrobial agents was performed by various well-established cell-based methods. Results. Compounds 6d and 5a showed promising biological screening data. The amidation of 3-benzoxazolyl aniline 1 with the chloroacetyl functional group resulted in a good antimalarial activity and showed moderate inhibitory activities against leishmanial and trypanosomal spp. Moreover, chloroacetyl functionalization of benzoxazolyl aniline serves as a good early goal for constructing and synthesizing new antimicrobial and antiprotozoal agents. The molecular docking study rationalizes the relative inhibitory activity of compound 5a as an antimalarial agent with the deregulation of PfPNP activity which has emerged as a major mechanism of these targets.

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Section: Antiprotozoal Activitymentioning

confidence: 99%

New Benzoxazole Derivatives as Antiprotozoal Agents: In Silico Studies, Synthesis, and Biological Evaluation

Abdelgawad

Al-Sanea

Zaki

et al. 2021

Journal of Chemistry

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“…The imported protein structure obtained from the PDB was not suitable for immediate use in the molecular docking study as it contained excess material (i.e., water molecules, metal ions, cofactors, etc.). To overcome this obstacle, the protein structure was prepared using the protein preparation wizard (preprocessed, optimized, and minimized) in Maestro v10.6 11,12 . The ligand structures of the data set were prepared by LigPrep module of Schrodinger v10.6 12 .…”

Section: Molecular Modelingmentioning

confidence: 99%

ACE inhibitor, captopril, attenuates cytopathic effects of herpes simplex virus 1 in SH-SY5Y cells

et al. 2020

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Background: Over 60% of the United States population is infected with herpes simplex virus 1 (HSV-1). Current HSV-1 treatment regimens exert their antiviral effects through a common mechanism of action and suffer from high dosing frequencies, which may contribute to patient noncompliance and the subsequent development of antiviral resistance. Although primarily known for their functions in maintaining homeostatic control of arterial blood and osmotic pressures, components of the Renin-Angiotensin Aldosterone System (RAAS) have been implicated in viral replication and some components demonstrated antiviral properties. However, the antiviral properties of RAAS components have not been well characterized in reference to HSV-1. Methods: To address this gap in knowledge, we evaluated the antiviral effects of captopril, an Angiotensin Converting Enzyme 1 (ACE-1) inhibitor, on HSV-1 infection in SH-SY5Y neuroblastoma cells. We demonstrated that captopril attenuates HSV-1-induced cytopathic effects (CPE) via cell-based and morphological assays. To investigate the potential mechanism, we conducted molecular modeling studies and identified the ability of captopril to interact with and bind HSV-1 glycoprotein D. To determine where in the virus life cycle captopril exerts its protective effects, we performed experiments observing the effect of captopril on both viral entry and replication utilizing a green fluorescent protein-tagged virus and subsequent quantitative Polymerase Chain Reaction. Results: Results suggest captopril protects cells from HSV-1-induced CPE through its effect on viral replication by increasing cell viability in infected cells and decreasing virus replication, which we propose is modulated through the decreased expression of ICP0. Conclusions: Collectively, the results presented here support further evaluation of captopril, and other RAAS components, as a basis for potential novel therapeutic interventions for the treatment of HSV-1, its associated pathologies, and potentially other virus infections.

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“…An about ten physically significant descriptors and pharmacological parameters of the ligands were analyzed. The water solubility of the ligand/compounds is playing a significant role in absorption, distribution, metabolism, excretion and the bioavailability [21,22]. The bioavailability of a molecule will be predicted using the Lipinski's rule of five, which is a familiar filter of choice.…”

Section: Adme Predictionmentioning

confidence: 99%

Assessing the Specificity of Paclitaxel towards the Marker Proteins of Breast Cancer Using In silico Molecular Docking Study

Kumar

Kumar²,

Parthasarathy

2020

JPRI

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Breast cancer is highly prevalent next to lung cancer. Breast cancer occurs as a result of mutation in the genes like proto-oncogenes as well as tumor suppressor genes in a single clone of cells in the ductal and glandular regions of the breast. The drugs used to prevent breast cancer are Raloxifene hydrochloride and Tamoxifen citrate. The drugs used to treat breast cancer are Abemaciclib, Paclitaxel, Everolimus, Imatinib, Alpelisib, Anastrozole. Although several drug molecules had been developed, their specificity towards the potential breast cancer specific marker proteins such as activated threonine kinase 2/Protein kinase B (AKT2), cell division protein kinase 6 (CDK6), estrogen receptor (ER), human epidermal growth factor receptor type 2 (HER2), and poly ADP ribose polymerase1 (PARP1) need to be studied in silico. The present study was undertaken 1) to assess the specificity of paclitaxel towards the breast cancer specific marker proteins using molecular docking analysis and 2) to identify various physico-chemical properties of drug molecules including absorption, distribution, metabolism and excretion (ADME). The interaction between paclitaxel and the target proteins of breast cancer was analyzed using the Schrodinger Maestro Ver.2018.4. The results of the present study reveal that paclitaxel shows good binding interactions with the target proteins in the following order, ER > PARP1 > AKT2 >CDK6 > HER2. Among the five proteins, ER and PARP1 showed good binding interactions as compared to AKT2, CDK6 and HER2 proteins. The ADME properties of paclitaxel were predicted using QikProp module of Schrodinger Maestro version 2018.4. The present study warrant further studies which helps in the development of potent anticancer drug to treat breast cancer.

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In-silico molecular design of heterocyclic benzimidazole scaffolds as prospective anticancer agents

Cited by 48 publications

References 38 publications

New Benzoxazole Derivatives as Antiprotozoal Agents: In Silico Studies, Synthesis, and Biological Evaluation

New Benzoxazole Derivatives as Antiprotozoal Agents: In Silico Studies, Synthesis, and Biological Evaluation

ACE inhibitor, captopril, attenuates cytopathic effects of herpes simplex virus 1 in SH-SY5Y cells

Assessing the Specificity of Paclitaxel towards the Marker Proteins of Breast Cancer Using In silico Molecular Docking Study

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