Design, synthesis, anti-tobacco mosaic viral and molecule docking simulations of urea/thiourea derivatives of 2-(piperazine-1-yl)-pyrimidine and 1-(4-Fluoro/4-Chloro phenyl)-piperazine and 1-(4-Chloro phenyl)-piperazine – A study

Nagalakshmamma, Vadabingi; Venkataswamy, M.; Pasala, Chiranjeevi; Umamaheswari, Amineni; Kedam, Thyaga Raju; Nagaraju, C.; Chalapathi, P. V.

doi:10.1016/j.bioorg.2020.104084

Cited by 22 publications

(12 citation statements)

References 28 publications

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“…The molecular docking and molecular dynamics simulations were used to understand the interaction between the TMV coat protein and the synthesized compounds. A good agreement was found between the in silico analysis and the experimental results [28]. However, there is an urgent need to find a new anti-TMV agent that is capable of preventing such a disease.…”

Section: Introductionsupporting

confidence: 64%

“…Research has continued to find potential alternative pesticides that do not pose a hazard to the environment [23][24][25][26][27]. Few in silico studies related to the TMV have been conducted [28][29][30]. For example, a series of ureas and thioureas containing heterocyclic compounds (e.g., pyrimidine and piperazine moieties) were studied to investigate their TMV inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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In Silico Pesticide Discovery for New Anti-Tobacco Mosaic Virus Agents: Reactivity, Molecular Docking, and Molecular Dynamics Simulations

et al. 2022

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Considerable data are available regarding the molecular genetics of the tobacco mosaic virus. The disease caused by the tobacco mosaic virus is still out of control due to the lack of an efficient functional antagonist chemical molecule. Extensive research was carried out to try to find effective new anti-tobacco mosaic virus agents, however no study could find an effective agent which could completely inhibit the disease caused by the virus. In recent years, molecular docking, combined with molecular dynamics, which is considered to be one of the most important methods of drug discovery and design, were used to evaluate the type of binding between the ligand and its protein enzyme. The aim of the current work was to assess the in silico anti-tobacco mosaic virus activity for a selection of 41 new and 2 reference standard compounds. These compounds were chosen to examine their reactivity and binding efficiency with the tobacco mosaic virus coat protein (PDB ID: 2OM3). A comparison was made between the activity of the selected compounds and that for ningnanmycin and ribavirin, which are common inhibitors of plant viruses. The simulation results obtained from the molecular docking and molecular dynamics showed that two compounds of the antofine analogues could bind with the tobacco mosaic virus coat protein receptor better than ningnanmycin and ribavirin.

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Section: Introductionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

In Silico Pesticide Discovery for New Anti-Tobacco Mosaic Virus Agents: Reactivity, Molecular Docking, and Molecular Dynamics Simulations

et al. 2022

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“…The final 1,3-disubstituted thioureas 1-12 were synthesized in a single-step reaction of 3-(trifluoromethyl)aniline with various isothiocyanates, belonging to a group of dihalogenophenyl (1-4), halogenomethylphenyl (5, 6), alkylphenyl (12), or monophenylsubstituted (7)(8)(9)(10)(11) derivatives (Scheme 1). The presented selection of the phenyl ring terminal groups allowed an investigation of the impact of the substitution isomerism, as well as the influence of the electron-withdrawing elements attached to the benzene ring on the biological properties within the tested thiourea series.…”

Section: Chemistrymentioning

confidence: 99%

“…By analogy, the replacement of the ortho-substituted CF 3 group (7) for the para (8) position was much more fruitful. While an exchange of this voluminous substituent for chlorine (8 → 9) still gave a strongly active analog, switching it into the cyano (10) or bromo (11) group considerably diminished the antitumor effect. Finally, the introduction of the unsubstituted alkylphenyl group (12) to the thiourea branch dramatically decreased the compound's bioactivity.…”

Section: Biological Studies 221 Cytotoxic Activitymentioning

confidence: 99%

“…The (thio)urea branch is an element of several medicines with anticancer profiles, such as sorafenib, multikinase-inhibitory diarylthiorea derivative, or tenovin-1, the benzylthiourea, which acts as a reversible inhibitor of class III HDAC sirtuins (Figure 1). On the other hand, it was reported that (hetero)aryl terminal fragments of thiourea moiety, enriched with electron-negative substituents, could provide biological responses, not only cytotoxic [2][3][4], but also antibacterial [2][3][4][5][6][7][8], antiviral [2,[9][10][11][12], antimycobacterial [5,13], antioxidant [14], and anti-inflammatory [6] properties, as well as central nervous system activation [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives

et al. 2021

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Substituted thiourea derivatives possess confirmed cytotoxic activity towards cancer but also normal cells. To develop new selective antitumor agents, a series of 3-(trifluoromethyl)phenylthiourea analogs were synthesized, and their cytotoxicity was evaluated in vitro against the cell line panel. Compounds 1–5, 8, and 9 were highly cytotoxic against human colon (SW480, SW620) and prostate (PC3) cancer cells, and leukemia K-562 cell lines (IC50 ≤ 10 µM), with favorable selectivity over normal HaCaT cells. The derivatives exerted better growth inhibitory profiles towards selected tumor cells than the reference cisplatin. Compounds incorporating 3,4-dichloro- (2) and 4-CF3-phenyl (8) substituents displayed the highest activity (IC50 from 1.5 to 8.9 µM). The mechanisms of cytotoxic action of the most effective thioureas 1–3, 8, and 9 were studied, including the trypan blue exclusion test of cell viability, interleukin-6, and apoptosis assessments. Compounds reduced all cancerous cell numbers (especially SW480 and SW620) by 20–93%. Derivatives 2 and 8 diminished the viability of SW620 cells by 45–58%. Thioureas 1, 2, and 8 exerted strong pro-apoptotic activity. Compound 2 induced late apoptosis in both colon cancer cell lines (95–99%) and in K-562 cells (73%). All derivatives acted as inhibitors of IL-6 levels in both SW480 and SW620 cells, decreasing its secretion by 23–63%.

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Ursolic acid regulates key EMT transcription factors, induces cell cycle arrest and apoptosis in MDA‐MB‐231 and MCF‐7 breast cancer cells, an in‐vitro and in silico studies

Mallepogu,

Sankaran,

Pasala

et al. 2023

J of Cellular Biochemistry

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Epithelial–mesenchymal transition (EMT) is a vital process in tumorigenesis and metastasis of breast cancer. In our quest to explore effective anticancer alternatives, ursolic acid (UA) was purified from Capparis zeylanica and investigated for its anticancer activity against MDA‐MB‐231 and MCF‐7 breast cancer cells. The apparent anticancer activity of UA on MDA‐MB‐231 and MCF‐7 cells was evident from IC50 values of 14.98 and 15.99 μg/mL, respectively, in MTT assay and also through enhanced generation of ROS. When MDA‐MB‐231 and MCF‐7 cells were treated with 20 μg/mL UA, an absolute decrease in cell viability of 47.6% and 48.6%, enhancement of 1.35% and 1.10% in early apoptosis, and 21.90% and 21.35% in late apoptosis, respectively and G0/G1 phase, S phase, G2/M phase cell cycle arrest was noticed. The gene expression studies revealed that UA could significantly (p < 0.001) downregulate the expression of EMT markers such as snail, slug, and fibronectin at molecular level. Further, the obtained in vitro results of snail, slug, and fibronectin were subjected to quantum‐polarized‐ligand (QM/MM) docking, which predicted that the in silico binding affinities of these three markers are in good correlation with strong hydrogen and van der Waal interactions to UA with −53.865, −48.971 and −40.617 MMGBSA (ΔGbind) scores, respectively. The long‐range molecular dynamics (50 ns) simulations have showed more consistency by UA. These findings conclude that UA inhibits breast cancer cells growth and proliferation through regulating the expression of key EMT marker genes, and thus UA is suggested as a potential anticancer agent.

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Design, synthesis, anti-tobacco mosaic viral and molecule docking simulations of urea/thiourea derivatives of 2-(piperazine-1-yl)-pyrimidine and 1-(4-Fluoro/4-Chloro phenyl)-piperazine and 1-(4-Chloro phenyl)-piperazine – A study

Cited by 22 publications

References 28 publications

In Silico Pesticide Discovery for New Anti-Tobacco Mosaic Virus Agents: Reactivity, Molecular Docking, and Molecular Dynamics Simulations

In Silico Pesticide Discovery for New Anti-Tobacco Mosaic Virus Agents: Reactivity, Molecular Docking, and Molecular Dynamics Simulations

Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives

Ursolic acid regulates key EMT transcription factors, induces cell cycle arrest and apoptosis in MDA‐MB‐231 and MCF‐7 breast cancer cells, an in‐vitro and in silico studies

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