Isolation, Characterization and Preliminary Cytotoxic and Antifungal Evaluations of Novel Lancifoliate Isolated from Methanol Extract of Conocarpus lancifolius

2020 ◽  
Vol 20 (14) ◽  
pp. 1664-1672
Author(s):  
Malik Saadullah ◽  
Muhammad Asif ◽  
Bashir A. Ch ◽  
Hafiza S. Yaseen ◽  
Muhammad Uzair ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cytotoxic Activity ◽  
Lymphocytic Leukemia ◽  
Proton Nuclear Magnetic Resonance ◽  
Human Lung Cancer ◽  
Spectroscopic Techniques ◽  
Human Colon Cancer ◽  
Skin Sample ◽  
Isolated Compound

Background: Combretaceae is a large family comprising of 500 species and 20 genera distributed in subtropical and tropical regions of the world. Conocarpus genus is an ornamental tree native to coastal and riverine areas of East Africa and is also planted as an ornamental plant in different areas of Pakistan. This genus has proved medicinal value as a cytotoxic, antibacterial, antiprotozoal, anti-leishmanial, antifungal and antidiabetic agent. Objective: The current study was designed to screen the selected pharmacological attributes of sulphur containing novel compound isolated from Conocarpus lancifolius using a series of in vitro and molecular docking models. Materials and Methods: After collection and authentication of plant material, methanolic extract was prepared from which various secondary metabolites were qualitatively examined. The compound was isolated using open column chromatography and the structure was established with spectroscopic techniques such as UV-visible, infrared spectroscopy, proton nuclear magnetic resonance (1H-NMR), 13C NMR (BB, DEPT-135, 90), twodimensional correlation techniques (HMBC, HSQC) and mass spectrometry (HRMS) respectively. C. lancifolius extract and isolated compound were studied for cytotoxic and antifungal potentials using in vitro Sulforhodamine B (SRB) and disc diffusion methods, respectively. Molecular docking studies were conducted to check the interaction of the isolated compound with major oncogenic proteins. Results: Qualitative phytochemical screening revealed the presence of saponins, steroids, flavonoids, anthraquinones, and cardiac glycosides while alkaloids were absent in C. lancifolius extract. Isolated compound was characterized as lancifoliate, which showed cytotoxic activity towards a variety of cancer cell lines including murine lymphocytic leukemia (P-388, IC50 = 2.65μg/ml), human colon cancer (Col-2, IC50 = 0.84μg/ml), human breast cancer (MCF-7, IC50 = 0.72μg/ml) while no cytotoxic activity was observed towards human lung cancer (Lu-1), rat normal glioma cells (ASK, IC50 = 11.6μg/ml) and human embryonic kidney cells (Kek293, IC50 = 6.74μg/ml) respectively. Minimum Inhibitory Concentration (MIC) of Lancifoliate towards Aspergillus fumigatus, Aspergillus nigar (skin sample), Aspergillus flavus (pleural fluid) and Candida albicans (urine and blood samples) was found to be 54.5, 44.8, 43.5, 22.4 and 20.2μg/ml respectively. Moreover, docking results are in strong agreement with our experimental finding, which has identified lancifoliate to be a more potent antiproliferative agent than previously known compound ellipticine. Conclusion: C. lancifolius extract and lancifoliate possess potent cytotoxic and antifungal properties and thus has potential to be further studied. To the best of our knowledge, this is the first study that highlights isolation, identification and pharmacological activities of lancifoliate from Conocarpus lancifolius.

scholarly journals Phytochemical and Molecular Dynamic Analysis of Novel Biomolecule Lancifotarene Extracted From Conocarpus Lancifolius as Cytotoxic, Antiurease and Antidiabetic Agent

2021 ◽  
Author(s):  
Malik Saadullah ◽  
Muhammad Asif ◽  
Shabana Bibi ◽  
Muhammad Ajmal Shah ◽  
Tahir Ali Chohan ◽  
...  
Keyword(s):  
Molecular Dynamic ◽  
Antioxidant Properties ◽  
Human Colon ◽  
Lymphocytic Leukemia ◽  
Human Lung Cancer ◽  
Dynamic Simulations ◽  
Human Colon Cancer ◽  
Human Embryonic Kidney Cells ◽  
Experimental Findings

Abstract A systematic study is designed to evaluate medicinal effects of dichloromethane extract and a novel compound from Conocarpus lancifolius which belongs to Family Combretaceae. Pharmacological experimental and computational analysis is performed for evaluation of anticancer, antidiuretic, alpha-glycosidase and antioxidant properties. Pharmacological potential of C. lancifolius extract and novel compound was determined for cytotoxic, antidiuretic, alpha glycosidase and antioxidant by using in vitro experimental analysis. Isolated novel compound lancifotarene showed cytotoxicity towards cancer cell lines including murine lymphocytic leukemia (P-388, IC50 = 2.65 μg/ml), human colon cancer (Col-2, IC50 = 0.84 μg/ml), human breast cancer (MCF-7, IC50 = 0.72 μg/ml), while no cytotoxicity observed towards human lung cancer (Lu-1), rat normal glioma cells (ASK, IC50 = 11.6 μg/ml) and human embryonic kidney cells (Kek293, IC50 = 6.74 μg/ml). Percentage inhibition at 0.5 mM of lancifotarene towards Urease inhibition was 66.54 ± 0.26 with IC50 = 162.70 ± 0.21 μM, and 82.58 ± 0.19 with IC50 = 72.45 ± 0.20 μM towards α-glucosidase inhibition. Molecular docking and molecular dynamic simulations reveal the stability of complexes by evaluation of root mean square deviation which correlate with the experimental findings, and identified lancifotarene as potential anti-proliferative, urease and alpha-glucosidase inhibitory agent.

Novel Ag(I)-NHC complex: synthesis, in vitro cytotoxic activity, molecular docking, and quantum chemical studies

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Goncagül Serdaroğlu ◽  
Neslihan Şahin ◽  
Serap Şahin-Bölükbaşı ◽  
Elvan Üstün
Keyword(s):  
Molecular Docking ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Quantum Chemical ◽  
Cancer Biology ◽  
Frontier Molecular Orbital ◽  
Cytotoxic Activities ◽  
Spectroscopic Techniques

Abstract The importance of organometallic complexes in cancer biology has attracted attention in recent years. In this paper, we look for the in vitro cytotoxic capability of novel benzimidazole-based N-heterocyclic carbene (NHC) precursor (1) and its Ag(I)-NHC complex (2). For this purpose, these novel Ag(I)-NHC complex (2) was characterized by spectroscopic techniques (1H, 13C{1H} nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FT-IR)). Then, in vitro cytotoxic activities of NHC precursor (1) and Ag(I)-NHC complex (2) were investigated against MCF-7, MDA-MB-231 human breast, DU-145 prostate cancer cells, and L-929 healthy cells using MTT assay for 24, 48, and 72 h incubation times. Ag(I)-NHC complex (2) showed promising in vitro cytotoxic activity against all cell lines for three incubation times, with IC50 values lower than 5 µM. It was also determined that (NHC) precursor (1) were lower in vitro cytotoxic activity than Ag(I)-NHC complex (2) against all cell lines. Selectivity indexes (SIs) of Ag(I)-NHC complex (2) against cancer cells were found higher than 2 for 24 and 48 h incubation time. Besides, the electronic structure and spectroscopic data of the newly synthesized precursor and its Ag-complex have been supported by density functional theory (DFT) calculations and molecular docking analysis. After, the anticancer activity of these compounds has been discussed considering the results of the frontier molecular orbital analysis. We hope that the obtained results from the experiments and computational tools will bring a new perspective to cancer research in terms of supported by quantum chemical calculations.

scholarly journals Synthesis, antimalarial activity evaluation and molecular docking studies of some novel dispiro-1,2,4,5-tetraoxanes

2015 ◽  
Vol 10 (4) ◽  
pp. 917 ◽  
Author(s):  
Mukesh Kumar Kumawat ◽  
Dipak Chetia
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Resistant Strain ◽  
Antimalarial Activity ◽  
Binding Pocket ◽  
Docking Studies ◽  
Spectroscopic Techniques ◽  
Molecular Docking Studies ◽  
Activity Screening

<p class="Abstract">Seven novel dispiro-1,2,4,5-tetraoxane derivatives were synthesized and characterized by a number of analytical and spectroscopic techniques. The molecules were subsequently screened for in vitro antimalarial activity against chloroquine resistant strain of <em>Plasmodium falciparum</em> (RKL-9). At antimalarial activity screening, two compounds, namely 5d (MIC = 15.6 µg/mL or 64.5 µM) and 5f (MIC = 15.6 µg/mL or 54.6 µM) were found to be about 1.5 times more potent against chloroquine resistant strain-RKL-9 compared to chloroquine (MIC = 25.0 µg/mL or 78.3 µM). Molecular docking studies of potent ligands were also performed in cysteine protease binding pocket residues of falcipain-2 as a target protein.</p><p> </p>

scholarly journals IN VITRO CYTOTOXIC ACTIVITY OF ISOLATED COMPOUNDS FROM VIBURNUM PUNCTATUM BUCH-HAM EX D. DON

2016 ◽  
Vol 9 (1) ◽  
pp. 85
Author(s):  
A. Renjith Alex ◽  
K. Ilango
Keyword(s):  
Cytotoxic Activity ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Methanol Extract ◽  
Methanolic Extract ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Chloroform Methanol ◽  
Human Colon Cancer Cells

Objective: The main aim of the study was to screen the isolated compounds of Viburnum Punctatum for its in vitro anticancer activity and its percentage viability against HCT 15 (Human Colon Cancer Cells) Cell lines.Methods: Pet ether, Chloroform, Methanol and Aqueous extracts was prepared and assayed for the presence of phytochemicals. Two compounds were isolated from the methanol extract of Viburnum Punctatum by column chromatography such as ME1 (Quercetin) and ME2 (Kaemferol-3-glycoside) characterised by UV, IR, MS, 1H NMR and 13C NMR. The above isolated compounds were subjected to in vitro anticancer activity on HCT 15 cell lines was evaluated by Micro culture Tetrazolium (MTT) assay.Results: ME1 showed significant cytotoxic activity than the ME2 on HCT 15 cells with a percentage viability of 54.60 and 67.18 in the concentration of 10µg/ml and 50µg/ml respectively.Conclusion: On the basis of obtained results, ME1 and ME2 isolated from a methanolic extract of Viburnum Punctatum represent a new group of cytotoxic against HCT 15 Cell lines.

Design, synthesis, characterization, in vitro screening, molecular docking, 3D-QSAR, and ADME-Tox investigations of novel pyrazole derivatives as antimicrobial agents

2022 ◽  
Author(s):  
Mohammed CHALKHA ◽  
Mohamed Akhazzane ◽  
Fatima Zahrae Moussaid ◽  
Ossama Daoui ◽  
Asmae Nakkabi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antimicrobial Agents ◽  
3D Qsar ◽  
Spectroscopic Techniques ◽  
In Vitro Screening ◽  
Pyrazole Derivatives ◽  
Design Synthesis ◽  
Practical Procedure

In this work, we report the synthesis of some new pyrazole derivatives via an efficient and practical procedure. The structures of the obtained compounds were established using different spectroscopic techniques...

Design, Synthesis, Anticancer Evaluation, and Molecular Docking Studies of Novel Benzoxazole Linked 1,3,4-Oxadiazoles

2021 ◽  
Vol 21 ◽  
Author(s):  
Sushmitha Bujji ◽  
Praveen Kumar E ◽  
Sree Kanth Sivan ◽  
Manjunatha DH ◽  
Subhashini N.J.P.
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Research Work ◽  
Docking Simulation ◽  
Research Field ◽  
Spectroscopic Techniques ◽  
Cancer Disease ◽  
Amide Derivatives

Background: Cancer disease is making a serious concern globally. Global cancer occurrence is steadily increasing every year. There is always a persistent need to develop new anticancer drugs with reduced side effects or act synergistically with the existing chemotherapeutics. Objective: Benzoxazoles are fused bicyclic nitrogen and oxygen-containing heterocyclic compounds and are considered biologically privileged scaffolds. We designed a synthetic route to link the benzoxazoles with oxadiazoles resulting in a better pharmacophore for anticancer activity. Methods: A series of novel amide derivatives of benzoxazole linked 1,3,4-oxadiazoles (10a-j) were synthesized and characterized by 1H NMR, 13C NMR, and mass spectroscopic techniques. The biological properties of the compounds were screened in vitro against four different tumor cell lines. Results: The results suggest that the compound 10b having 3,4,5-trimethoxy substitution on the phenyl ring exhibited potent anticancer activity in three cell lines (A549 = 0.13 ± 0.014 µM, MCF-7 = 0.10 ± 0.013 µM and HT-29 = 0.22 ± 0.017 µM). Notably, among the synthesized derivatives, compounds 10b, 10c, 10f, 10g, and 10i exhibited potent anticancer activity than the control IC50 in the range of 0.11 ± 0.02 to 0.93 ± 0.034 µM. Molecular docking simulation results showed compounds were stabilized by hydrogen bond and π-π interactions with the protein. Conclusion: The molecules showed comparable binding affinities with standard Combretastatin-A4. The present research work is preliminary and needs further studies to take the synthesized compounds to the next level in the cancer research field.

BTK Inhibitors, Irrespective of ITK Inhibition, Increase Efficacy of a CD19/CD3 Bispecific Antibody in CLL

Blood ◽  
2021 ◽  
Author(s):  
Maissa Mhibik ◽  
Erika M. Gaglione ◽  
David Eik ◽  
Ellen K Kendall ◽  
Amy Blackburn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic Activity ◽  
Kinase Inhibitors ◽  
Bispecific Antibody ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Lymphocytic Leukemia ◽  
Peripheral Blood Mononuclear

Bruton Tyrosine Kinase inhibitors (BTKis) are a preferred treatment for patients with chronic lymphocytic leukemia (CLL). Indefinite therapy with BTKis, while effective, presents clinical challenges. Combination therapy can deepen responses, shorten treatment duration, and possibly prevent or overcome drug resistance. We previously reported on a CD19/CD3 bispecific antibody (bsAb) that recruits autologous T cell cytotoxicity against CLL cells in vitro. Compared to observations with samples from treatment-naïve patients, T cells from patients being treated with ibrutinib expanded more rapidly and exerted superior cytotoxic activity in response to the bsAb. In addition to BTK, ibrutinib also inhibits IL2 inducible T cell Kinase (ITK). In contrast, acalabrutinib, does not inhibit ITK. Whether ITK inhibition contributes to the observed immune effects is unknown. To better understand how BTKis modulate T-cell function and cytotoxic activity, we cultured peripheral blood mononuclear cells (PBMCs) from BTKi-naive, and ibrutinib- or acalabrutinib-treated CLL patients with CD19/CD3 bsAb in vitro. T-cell expansion, activation, differentiation, and cytotoxicity were increased in PBMCs from patients on treatment with either BTKi compared to that observed for BKTi-naïve patients. BTKi therapy transcriptionally downregulated immunosuppressive effectors expressed by CLL cells, including CTLA-4 and CD200. CTLA-4 blockade with ipilimumab in vitro increased the cytotoxic activity of the bsAb in BTKi-naïve but not BTKi-treated PBMCS. Taken together, BTKis enhance bsAb induced cytotoxicity by relieving T cells of immunosuppressive restraints imposed by CLL cells. The benefit of combining bsAb immunotherapy with BTKis needs to be confirmed in clinical trials.

Synthesis, characterization, in vitro cytotoxic activity and molecular docking of dinuclear gold(I) complexes with terephthalaldehyde bis(thiosemicarbazones)

Polyhedron ◽  
2021 ◽  
Vol 210 ◽  
pp. 115498
Author(s):  
Ignacio del Águila ◽  
M. Antonia Mendiola ◽  
Sayantan Pradhan ◽  
Chittaranjan Sinha ◽  
Elena López-Torres
Keyword(s):  
Molecular Docking ◽  
Cytotoxic Activity

scholarly journals Synthesis of Novel 1,2,4-Triazolyl Coumarin Derivatives as Potential Anticancer Agents

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Lamya H. Al-Wahaibi ◽  
Hanaa M. Abu-Melha ◽  
Diaa A. Ibrahim
Keyword(s):  
Colon Cancer ◽  
Molecular Docking ◽  
Anticancer Agents ◽  
Tyrosine Kinases ◽  
Hct116 Cell ◽  
Human Colon ◽  
Docking Studies ◽  
Coumarin Derivatives ◽  
Human Colon Cancer

A series of novel coumarin derivatives carrying 1,2,4-triazole or 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole moieties were prepared and evaluated in vitro as anticancer in the human colon cancer (HCT116) cell line. The derivatives 4c and 8c exhibited marked anticancer activity with IC50 values 4.363 and 2.656 µM, respectively. The molecular docking studies suggested possible interaction with tyrosine kinases (CDK2).

scholarly journals Cytotoxic Pentacyclic Triterpenoids from Combretum oliviforme

2010 ◽  
Vol 5 (7) ◽  
pp. 1934578X1000500
Author(s):  
Xiao-Peng Wu ◽  
Chang-Ri Han ◽  
Guang-Ying Chen ◽  
Yuan Yuan ◽  
Jian-Ying Xie
Keyword(s):  
Cytotoxic Activity ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Human Lung Cancer ◽  
Ionization Mass ◽  
Human Gastric Cancer ◽  
Pentacyclic Triterpenoids ◽  
Acetyl Group ◽  
First Time

Four pentacyclic triterpenoids were obtained from the leaves of Combretum oliviforme Chao, 3β–hydroxyolean–12–en–28–oic acid (1), 23– O–[α-L-(4′-acetylrhamnopyranosyl)]–imberbic acid (2), 23–acetoxy–3β–acetylimberbic acid–29–methyl ester (3), and 23– O–[α-L-rhamnopyranosyl]-1,3β-diacetylimberbic acid (4). Hydrolysis of 2 and 4 gave 23–hydroxyimberbic acid (5). The structures were elucidated by NMR, electrospray ionization mass spectrometry (ESIMS) and comparison with literature data. Compounds 1, 2, 3 and 4 were isolated from C. oliviforme Chao leaves for the first time and 3 for the first time from any natural source. All compounds were tested in vitro for their activity against human lung cancer cell line SPC-A-1, human erythroleukaemic line K562 and human gastric cancer SGC-7901 cells. Compounds 1, 3, 4 and 5 had cytotoxic activity for the three cell lines with IC50 0.69-69.68 μM. These results suggest that the presence of acetyl group in the triterpene aglycone structure plays an essential role for cytotoxic activity.

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