Effective Pharmacophore for CDC25 Phosphatases Enzyme Inhibitors: Newly Synthesized Bromothiazolopyrimidine Derivatives

2020 ◽  
Vol 20 ◽  
Author(s):  
Mahmoud El-Shahat ◽  
Mowafia A.M. Salama ◽  
Ahmed F. El-Farargy ◽  
Mamdouh M. Ali ◽  
Dalia M. Ahmed
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Enzyme Inhibitors ◽  
Wide Spectrum ◽  
Hct116 Cell ◽  
Cytotoxic Activities ◽  
The Novel ◽  
Anticancer Activities ◽  
Starting Compound

Background: Thiazolopyrimidine analogues are versatile synthetic scaffold possessing wide spectrum of biological interests involving potential anticancer activity. Objective: To report the synthesis of novel bromothiazolopyrimidine derivatives and the study of both molecular modeling and in-vitro anticancer activity. Method: Novel bromothiazolopyrimidine derivatives 5–18 have been prepared from 2-bromo-3-(4-chlorophenyl)-1-(3,4- dimethylphenyl)-propenone 3 as a key starting compound. The anti-cancer activities of the new compounds were evaluated against HepG2, MCF-7, A549 and HCT116 cell lines. Results: The compounds 16, 17 and 18 showed cytotoxic and growth inhibitory activities on both colon and lung cells. The cytotoxic activities of the novel synthetic compounds 8, 9, 11, 16, 17 and 18 were due to CDC25 phosphatases inhibition as shown by the enzymatic binding assay. Although compounds 8, 9 and 11 have only demonstrated CDC25B phosphatases inhibition. Conclusion: The novel bromothiazolopyrimidine derivatives showed promising in vitro anticancer activities against colon cancer HCT116 and lung cancer A549 cell lines comparable to the anticancer drug doxorubicin.

Novel Pyrazolyl Benzoxazole Conjugates: Design, Synthesis, Molecular Docking Studies and in vitro Anticancer Activities

2019 ◽  
Vol 16 (8) ◽  
pp. 619-626
Author(s):  
Arunkumar Thiriveedhi ◽  
Ratnakaram Venkata Nadh ◽  
Navuluri Srinivasu ◽  
Narayana Murthy Ganta
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Docking Studies ◽  
Anticancer Activities ◽  
Molecular Docking Studies ◽  
Hybrid Molecules ◽  
Mcf 7

Nowadays, hybrid drugs have gained a significant role in the treatment of different health problems. Most of the hybrid molecules with different heterocyclic moieties were proved to be potent anti-tumor agents in cancer chemotherapy. Hence, the present study is aimed at the evaluation of in vitro anticancer activity of novel hybrid molecules (pyrazolyl benzoxazole conjugates) and to investigate their anticancer activity by molecular docking studies. Designed, synthesized and characterized the novel pyrazolyl benzoxazole conjugates. Anticancer activity of these compounds was determined by SRB assay. Then molecular docking studies were carried out against proto-oncogene tyrosine-protein kinase (ATP-Src, PDB: 2BDF), a putative target for cancer. All the synthesized compound derivatives were evaluated against MCF-7, KB, Hop62 and A549 cancer cell lines. Compounds 9b and 9c exhibited excellent anticancer activities with GI50 values of <0.1 µM against MCF-7 and A549 cell lines. Compound 9e exhibited good antitumor activity on MCF-7 and A-549 with GI50 values of 0.12 µM and 0.19 µM respectively. Compound 9g showed better anticancer activity on A-549 cancer cell line with GI50 of 0.34 µM. The two-hybrid molecules 9b and 9c are found to be comparably potent with the standard drug doxorubicin and may act as drug lead compounds in medicinal chemistry aspect. The present docking investigation proved that having benzoxazole of compound 9c at the position of benzofuran of reference compound (N-acetyl pyrazoline derivative) might be valid for contributing to anti-cancer activity.

Novel Tetrahydrobenzo [b] Thiophene Compounds Exhibit Anticancer Activity through Enhancing Apoptosis and Inhibiting Tyrosine Kinase

2019 ◽  
Vol 18 (12) ◽  
pp. 1761-1769 ◽  
Author(s):  
Souad A. El-Metwally ◽  
Ali K. Khalil ◽  
Abeer M. El-Naggar ◽  
Wael M. El-Sayed
Keyword(s):  
Tyrosine Kinase ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Hct116 Cell ◽  
Parent Compound ◽  
Chemotherapeutic Agents ◽  
Cytotoxic Activities ◽  
Standard Drug ◽  
Reference Drug

Background: Developing new chemotherapeutic agents with molecular targets, larger margin of safety against normal cells and low cost is the target many scientists try to achieve. Objective: The present study was undertaken to investigate the anticancer activity of a novel series of thiophene compounds and the molecular mechanisms associated. Method: A series of novel heterocyclic compounds including pyrimidine derivatives (2, 3, 4, 5 8, 11, 12, 13, 14, and 15), thiophene derivatives (6, 7, and 10) and oxoisothiazolidine derivative (9) was synthesized from 4,5,6,7- tetrahydrobenzo[b] thiophene (1). The newly synthesized derivatives along with the parent compound were evaluated for their anticancer activity against human HepG2, MCF7 and HCT116 cell lines and compared to doxorubicin as a reference drug. Results: Compound 7 was very selective in targeting only the colon cells. Compounds 1, 5, and 12 showed strong cytotoxic activities against the 3 cell lines at 6-16 µM without any apparent toxicity to the normal fibroblasts WI-38. They had DNA affinity at 29-36 µM. The three compounds enhanced apoptosis to varying degrees elevating the expression of Bax, caspase 9 and caspase 3 in HepG2. Compound 5 was the most potent analogue and was superior to the standard drug used in upregulating the apoptotic genes and inhibiting tyrosine kinase at 1 µM. The IC50 value for compound 5 against TK was 296 nM. Conclusion: Taken together, this study presents some thiophene scaffolds as auspicious hits for further optimization as specific antiproliferative agents against cancer cells and promising tyrosine kinase inhibitors at nanomolar concentrations.

Synthesis of novel 1,4-disubstituted 1,2,3-triazolo-bosentan derivatives – evaluation of antimicrobial and anticancer activities and molecular docking

RSC Advances ◽  
2015 ◽  
Vol 5 (127) ◽  
pp. 105266-105278 ◽  
Author(s):  
K. Easwaramoorthi ◽  
A. Jeya Rajendran ◽  
K. Chennakesava Rao ◽  
Y. Arun ◽  
C. Balachandran ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Anticancer Activities ◽  
One Pot ◽  
One Pot Synthesis

One pot synthesis with good yields. Good antimicrobial activity against 4EMV receptor. Prominent anticancer activity against A549 and SKOV-3 cell lines. Significantin vitrocytotoxicity at 7.81 μg mL−1. Docking mode of1hwith 2XP2 receptor.

Design, Synthesis and Cytotoxic Activity of Spiro(oxindole-3-3'- pyrrolidine) Derivatives

2018 ◽  
Vol 15 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Dilan Konyar ◽  
Cenk A. Andac ◽  
Erdem Buyukbingol
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Molecular Sieves ◽  
Intermediate Compound ◽  
Huh7 Cell ◽  
Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Anticancer Activities ◽  
Cytotoxicity Studies

Background: Spiro[pyrrolidine-3,3'-oxindole] compounds are reported to be highly bioactive natural and synthetic products. Initially, spirooxindole alkaloids were isolated from plants of the Apocynaceae and Rubiaceae families, which were found to have a common scaffold, spiro[pyrrolidine-3,3'-oxindole], exhibiting anticancer activities., we specifically aimed at the synthesis, characterization and anticancer activity of novel spiro[pyrrolidine-3,3' -oxindole] derivatives, compounds 6a-c and 7. Methods: The synthesis was initiated by Knovenegal condensation of indole-2-one with an appropriate benzaldehyde in presence of piperidine to afford compounds 3a-c. Compounds 6a-c were synthesized by an asymmetric 1,3-dipolar cycloaddition between compounds 3a-c and (2S, 3R)-2, 3, 5, 6-tetrahydro-2, 3-diphenyl-1, 4-oxazin-6-one, which is an intermediate compound formed by the Schiff base reaction between 3-methyl-butanal and (2S, 3R)-2, 3, 5, 6-tetrahydro-2, 3-diphenyl- 1,4-oxazin-6-one, in presence of molecular sieves (4Å) under argon atmosphere. Compound 6a was then reacted with ethylamine-HCl in THF at room temperature to yield compound 7. Results: Cytotoxic effects of the compounds synthesized were determined on Huh7, MV, HCT116 and MCF7 cancer cell lines by the NCI-60 Sulforhodamine B Assay, using (S)-(+)-Camptothecin as a positive control. In general, target compounds showed better cytotoxic activities against the MCF7 and HCT116 cancer cell lines. It was found that compound 7 exhibited the most potent inhibitory activity with IC50 values of 4.8 µM, 3.9 µM, 14.9 µM and 8.2 µM against the MCF7, HCT116, MV and Huh7 cell lines, respectively. Conclusion: It was determined that compounds 6a&6b possess C6'(S)|C8'(R)|C9'(R) stereochemistry and compound 7 adopts C2'(S)|C4'(R)|C5'(R) stereochemistry. Cytotoxicity studies suggest that compound 7 gave rise to the highest anticancer activity against MCF7, HCT116, and Huh7 cancer cell lines.

scholarly journals Novel Papaverine Metal Complexes with Potential Anticancer Activities

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5447
Author(s):  
Ahmed Gaber ◽  
Walaa F. Alsanie ◽  
Deo Nandan Kumar ◽  
Moamen S. Refat ◽  
Essa M. Saied
Keyword(s):  
Breast Cancer ◽  
Biological Activity ◽  
Metal Complexes ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Mcf 7

Cancer is one of the leading causes of death worldwide. Although several potential therapeutic agents have been developed to efficiently treat cancer, some side effects can occur simultaneously. Papaverine, a non-narcotic opium alkaloid, is a potential anticancer drug that showed selective antitumor activity in various tumor cells. Recent studies have demonstrated that metal complexes improve the biological activity of the parent bioactive ligands. Based on those facts, herein we describe the synthesis of novel papaverine–vanadium(III), ruthenium(III) and gold(III) metal complexes aiming at enhancing the biological activity of papaverine drug. The structures of the synthesized complexes were characterized by various spectroscopic methods (IR, UV–Vis, NMR, TGA, XRD, SEM). The anticancer activity of synthesized metal complexes was evaluated in vitro against two types of cancer cell lines: human breast cancer MCF-7 cells and hepatocellular carcinoma HepG-2 cells. The results revealed that papaverine-Au(III) complex, among the synthesized complexes, possess potential antimicrobial and anticancer activities. Interestingly, the anticancer activity of papaverine–Au(III) complex against the examined cancer cell lines was higher than that of the papaverine alone, which indicates that Au-metal complexation improved the anticancer activity of the parent drug. Additionally, the Au complex showed anticancer activity against the breast cancer MCF-7 cells better than that of cisplatin. The biocompatibility experiments showed that Au complex is less toxic than the papaverine drug alone with IC50 ≈ 111 µg/mL. These results indicate that papaverine–Au(III) complex is a promising anticancer complex-drug which would make it a suitable candidate for further in vivo investigations.

scholarly journals Pd(PPh3)4 Catalyzed Synthesis of Indazole Derivatives as Potent Anticancer Drug

2020 ◽  
Vol 10 (11) ◽  
pp. 3792
Author(s):  
Jagan Mohana Rao Saketi ◽  
S. N. Murthy Boddapati ◽  
Raghuram M. ◽  
Syed Farooq Adil ◽  
Mohammed Rafi Shaik ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Arylboronic Acids ◽  
Hct 116 ◽  
Methyl Derivatives

A series of 3-aryl indazoles and 1-methyl-3-aryl indazole derivatives are prepared with exceptional yields by coupling with several arylboronic acids and methylation by two dissimilar approaches. The as-prepared indazole derivatives (3a–3j) and their N-methyl derivatives (5a–5j) are evaluated for in vitro anticancer activity against two cancer cell lines, HCT-116 and MDA-MB-231. The results reveal that the indazole derivatives tested display mild to moderate anticancer activities against the cell lines tested.

scholarly journals Orchids as Potential Sources of Anticancer Agents: Our Experience

2021 ◽  
Vol 1 (1) ◽  
pp. 42-51
Author(s):  
Bijaya Pant ◽  
Mukti Ram Paudel ◽  
Pusp Raj Joshi
Keyword(s):  
Health Systems ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Financial Strain ◽  
In Vitro Assays ◽  
Cytotoxic Activities ◽  
Anticancer Activities ◽  
Orchid Species ◽  
Quality Diagnosis

Cancer is the second leading cause of death globally and the cancer burden continues to grow, exerting tremendous physical, emotional and financial strain on individuals, families, communities and health systems. Many health systems in low- and middle-income countries are ill-prepared to manage this burden, and around the world large numbers of cancer patients do not have access to timely quality diagnosis or treatment. Natural products, especially originated from plants, have been applied as remedies to treat various diseases, including cancer, for thousands of years. Several anticancer agents derived from plants, such as paclitaxel (taxol), vinblastine, vincristine, camptothecin derivatives, podophyllotoxins, are in clinical use and a number of other promising agents are in preclinical or clinical development. A growing number of bioactive compounds with cytostatic and cytotoxic activities to treat cancer have been isolated from several orchid species. The Annapurna Research Center in collaboration with other academic institutions is engaged in identifying and exploring anticancer compounds in orchids of Nepal. The center has identified ten different orchid species which contain high phenol and flavonoid contents evidently showing anticancer activities in our in vitro assays against different cancer cell lines viz cervical cancer, lung cancer and brain tumor cell lines. These findings demonstrate that orchids which have been used in in various formulations in traditional medicine since ancient times qualify as potential source for novel drug candidates or starting points for further lead optimization towards clinical candidates for the most urgently needed treatment of aggressive types of cancer. This review paper highlights that in all likelihood; our contributions in orchid research here in Nepal could bring great relief to patients with cancer globally.

Extraction, Chemical Composition, Antioxidant Property and In vitro Anticancer Activity of Silymarin from Silybum Marianum On Kb and A549 Cell Lines

2020 ◽  
Vol 17 ◽  
Author(s):  
Mojgan Azadpour ◽  
Mohammad Mehdi Farajollahi ◽  
Ali Mohammad Varzi ◽  
Pejman Hashemzadeh ◽  
Hossein Mahmoudvand ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
A549 Cell ◽  
Hplc Analysis ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Antioxidant Property ◽  
Silybum Marianum ◽  
Stable Free Radical

Introduction: This study aimed to evaluate the antioxidant property of silymarin (SM) extracted from the seed of Silybum marianum and its anticancer activity on KB and A549 cell lines following 24, 48, and 72 h of treatment. Methods: Ten grams of powdered S. marianum seeds were defatted using n-hexane for 6 hours and then extracted by methanol. The silymarin extracted of extraction components The extracted components of silymarin were measured by spectrophotometric assay and HPLC analysis. 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, phenol content, total flavonoid content, and total antioxidant capacity were measured to detect the antioxidant properties of SM. The anticancer activity of the SM on cell lines evaluated by MTT. Results: In HPLC analysis, more than 50% of the peaks were related to silibin A and B. SM was reducedDPPH (the stable free radical) with a 50% inhibitory concentration (IC50) of 6.56 μg/ ml in comparison with butylated hydroxyl toluene (BHT), which indicated an IC50 of ~3.9 μg/ ml.The cytotoxicity effect of SM on the cell lines was studied by MTT assay. The cytotoxicity effect of the extracted silymarin on KB and A549 cell lines was observed up to 80 and 70% at 156 and 78 µg/ml, respectively. The IC50 value of the extracted SM on KB and A549 cell lines after 24 hours of treatment was seen at 555 and 511 µg/ml, respectively. Conclusion: Due to the good antioxidant and anticancer properties of the isolated silymarin, its use as an anticancer drug is suggested.

(Substituted)-benzo[b]thiophene-4-carboxamide Synthesis and Antiproliferative Activity Study

2020 ◽  
Vol 17 (5) ◽  
pp. 563-573 ◽  
Author(s):  
Chandrakant Dhondiram Pawar ◽  
Dattatraya Navnath Pansare ◽  
Devanand Baburao Shinde
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Proliferative Activity ◽  
Thiophene Ring ◽  
Amide Group ◽  
Peptide Coupling ◽  
Ic50 Value ◽  
Important Building Block ◽  
Mcf 7

Background: Thiophene ring forms important building block in medicinal chemistry. Literature reveals that thiophene ring in combination with different groups shows different activity. By keeping these things in mind we have designed and synthesized a new series of amide and sulfonamide coupled thiophene. A series of novel substituted 3-sulfamoylbenzo[b]thiophene-4- carboxamide molecules containing sulfonamide and amide group were designed, synthesized and used for anti-proliferative activity study. Methods: The final compounds 16-36 were synthesized by using series of reactions comprising sulfonation, sulfonamide coupling, hydrolysis and peptide coupling. The yields of compounds 16- 36 are in the range of 90-98%. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR, LCMS and the purity was checked through HPLC analysis. The compounds were further tested for their in vitro anticancer activity against a series of cell lines A549, HeLa, MCF-7 and Du-145. Results: The intermediates 8-13, 15 and final compounds 16-36 were synthesized in good yields. The synthesized compounds were further tested for their anticancer activity and most of compounds showed moderate to good anticancer activity against all four cell lines. Conclusion: We have synthesized 21 compounds and were screened for anticancer activity against MCF-7, HeLa, A-549 and Du-145 cancer cell lines. Most of the compounds were active for tested cell lines with IC50 value in the range of 1.81 to 9.73 μM. The compounds 18, 19, 21, 25, 30, 31 and 33 are most active in cell line data with IC50 value in the range of 1.81 to 2.52 μM.

Anticancer Activity and Topoisomerase II Inhibition of Naphthalimides with ω-Hydroxylalkylamine Side-Chains of Different Lengths

2019 ◽  
Vol 15 (5) ◽  
pp. 550-560
Author(s):  
Mateusz D. Tomczyk ◽  
Anna Byczek-Wyrostek ◽  
Klaudia Strama ◽  
Martyna Wawszków ◽  
Przemysław Kasprzycki ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Topoisomerase Ii ◽  
Significant Activity ◽  
Anticancer Activities ◽  
Human Colon Cancer ◽  
Substitution Pattern ◽  
Topo Ii

Background: The substituted 1,8-Naphthalimides (1H-benzo[de]isoquinoline-1,3(2H)- diones) are known as DNA intercalators stabilizing DNA-Topoisomerase II complexes. This interaction disrupts the cleavage-relegation equilibrium of Topo II, resulting in formation of broken strands of DNA. Objective: To investigate the influence of type of substituents and substitution positions in 1,8- naphthalimde skeleton on the inhibition of Topoisomerase II activity. Methods: The starting 1,8-naphthalimide were prepared from acenaphthene by introduction of appropriate substituents followed by condensation with ω-hydroxylakylamines of different chain length. The substituents were introduced to 1,8-naphthalimide molecule by nucleophilic substitution of leaving groups like nitro or bromo present in 4 or 4,5- positions using the ω- hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines. Results: Antiproliferative activity of selected compounds against HCT 116 human colon cancer cells, human non-small cell lung cells A549 and non-tumorigenic BEAS-2B human bronchial epithelium cells was examined. Several of investigated compounds exhibit a significant activity (IC50 µM to 7 µM) against model cancer cell lines. It was demonstrated that upon treatment with concentration of 200 µM, all derivatives display Topo II inhibitory activity, which may be compared with activity of Amonafide. Conclusion: The replacement of the nitro groups in the chromophore slightly reduces its anticancer activities, whereas the presence of both nitro group and ω-hydroxylalkylamine chain resulted in seriously increased anticancer activity. Obtained compounds showed Topo II inhibitory activity, moreover, influence of the substitution pattern on the ability to inhibit Topo II activity and cancer cells proliferation was observed.

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