scholarly journals Pyrrolizine-5-carboxamides: Exploring the impact of various substituents on anti-inflammatory and anticancer activities

2018 ◽  
Vol 68 (3) ◽  
pp. 251-273 ◽  
Author(s):  
Ahmed M. Gouda ◽  
Ahmed H. Abdelazeem ◽  
Ashraf N. Abdalla ◽  
Muhammad Ahmed
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Inflammatory Activity ◽  
Electronic Effects ◽  
Anticancer Activities ◽  
Phenyl Rings ◽  
Anti Inflammatory ◽  
New Compounds ◽  
The Impact ◽  
Mcf 7

Abstract Towards optimization of the pyrrolizine-5-carboxamide scaffold, a novel series of six derivatives (4a-c and 5a-c) was prepared and evaluated for their anti-inflammatory, analgesic and anticancer activities. The (EZ)-7-cyano-6-((4-hydroxybenzylidene)amino)-N-(p-tolyl)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (4b) and (EZ)-6-((4-chlorobenzylidene)-amino)-7-cyano-N-(p-tolyl)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (5b) bearing the electron donating methyl group showed the highest anti-inflammatory activity while (EZ)-6-((4-chlorobenzylidene)amino)-7-cyano-N-phenyl-2,3-dihydro-1H-pyrrolizine-5-carboxamide (5a) was the most active analgesic agent. Cytotoxicity of the new compounds was evaluated against the MCF-7, A2780 and HT29 cancer cell lines using the MTT assay. Compounds 4b and 5b displayed high anticancer activity with IC50 in the range of 0.30–0.92 μmol L−1 against the three cell lines, while compound (EZ)-N-(4-chlorophenyl)-7-cyano-6-((4-hydroxybenzylidene)-amino)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (4c) was the most active against MCF-7 cells (IC50 = 0.08 μmol L−1). Both the anti-inflammatory and anticancer activities of the new compounds were dependent on the type of substituent on the phenyl rings. Substituents with opposite electronic effects on the two phenyl rings are preferable for high cytotoxicity against the MCF-7 and A2780 cells. COX inhibition was suggested as the molecular mechanism of the anti-inflammatory activity of the new compounds while no clear relationship could be observed between COX inhibition and anticancer activity. Compound 5b, the most active against the three cell lines, induced dose-dependent early apoptosis with 0.1–0.2 % necrosis in MCF-7 cells. New compounds showed promising drug-likeness scores while the docking study revealed high binding affinity to COX-2. Taken together, this study highlighted the significant impact of the substituents on the anti-inflammatory and anticancer activity of pyrrolizine-5-carboxamides, which could help in further optimization to discover good leads for the treatment of cancer and inflammation.

scholarly journals Aspirin-Based Organoiron Dendrimers as Promising Anti-Inflammatory, Anticancer, and Antimicrobial Drugs

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1568
Author(s):  
Alaa S. Abd-El-Aziz ◽  
Maysun R. Benaaisha ◽  
Amani A. Abdelghani ◽  
Rabin Bissessur ◽  
Laila H. Abdel-Rahman ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Inflammatory Activity ◽  
Breast Cancer Cell Lines ◽  
Cell Viability Assay ◽  
Reference Drug ◽  
Anti Inflammatory

Designing nanocarriers with actions directed at a specific organ or tissue is a very promising strategy since it can significantly reduce the toxicity of a bioactive drug. In this study, an organometallic dendrimer was used to synthesize a biocompatible drug delivery system by attaching aspirin to the periphery of the dendrimer. Our goal is to enhance the bioavailability and anticancer activity of aspirin and reduce its toxicity through successive generations of organoiron dendrimers. The biological activity of aspirin-based dendrimer complexes was evaluated. The result of antimicrobial activity of the synthesized dendrimers also demonstrated an increase in their antimicrobial activity with increased generation of the dendrimers for most types of microorganisms. This study reveals for the first time that organoiron dendrimers linked with aspirin exhibit an excellent Gram-negative activity comparable to the reference drug Gentamicin. All synthesized dendrimers were tested for their anticancer activity against breast cancer cell lines (MCF-7), hepatocellular cell lines (Hep-G2), and a non-cancer cell line, Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, Doxorubicin. Compounds G3-D9-Asp and G4-D12-Asp exhibited noticeable activity against both cell lines, both of which were more effective than aspirin itself. In addition, the in vivo anti-inflammatory activity and histopathology of swollen paws showed that the designed aspirin-based dendrimers displayed significant anti-inflammatory activity; however, G2-D6-Asp showed the best anti-inflammatory activity, which was more potent than the reference drug aspirin during the same period. Moreover, the coupling of aspirin to the periphery of organoiron dendrimers showed a significant reduction in the toxicity of aspirin on the stomach.

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.

scholarly journals Synthesis, Structural Characterization and Anticancer Activity of New 5-Trifluoromethyl-2-thioxo-thiazolo[4,5-d]pyrimidine Derivatives

2022 ◽  
Vol 15 (1) ◽  
pp. 92
Author(s):  
Lilianna Becan ◽  
Anna Pyra ◽  
Nina Rembiałkowska ◽  
Iwona Bryndal
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Screening Program ◽  
Human Cancer ◽  
3D Structure ◽  
X Ray Diffraction ◽  
Pyrimidine Derivatives ◽  
New Compounds ◽  
Mcf 7

Thiazolo[4,5-d]pyrimidine derivatives are considered potential therapeutic agents, particularly in the development of anticancer drugs. In this study, new 7-oxo-(2a-e), 7-chloro-(3a-e) and also three 7-amino-(4a-c) 5-trifluoromethyl-2-thioxo-thiazolo[4,5-d]pyrimidine derivatives have been synthesized and evaluated for their potential anticancer activity. These derivatives were characterized by spectroscopic methods and elemental analysis, and the single-crystal X-ray diffraction was further performed to confirm a 3D structure for compounds 2e and 4b. The antiproliferative activity evaluation of twelve new compounds was carried out on a variety of cell lines including four human cancer (A375, C32, DU145, MCF-7/WT) and two normal cell lines (CHO-K1 and HaCaT). Four of them (2b, 3b, 4b and 4c) were selected by the National Cancer Institute and evaluated for their in vitro anticancer activity using the NCI-60 screening program. 7-Chloro-3-phenyl-5-(trifluoromethyl)[1,3]thiazolo[4,5-d]pyrimidine-2(3H)-thione (3b) proved to be the most active among the newly synthesized compounds.

scholarly journals Biological activities of synthetic coumarin derivatives

2016 ◽  
Author(s):  
◽  
Kabange Kasumbwe
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Caspase 3 ◽  
Morphological Changes ◽  
Annexin V ◽  
Positive Control ◽  
Inflammatory Activity ◽  
Anti Cancer ◽  
Anti Inflammatory ◽  
Mcf 7

Coumarins are naturally occurring α-benzopyrone derivatives known for their pharmacological properties such as anticoagulant, antimicrobial, anticancer, antioxidant, anti-inflammatory and antiviral properties. The pharmacological, biochemical, and curative applications of coumarins depend on the substitution around the coumarin core structure. In the present study, seven halogenated coumarins CMRN1 - CMRN7 were synthesized and evaluated for mosquito larvicidal, repellancy , and insecticidal activity against Anopheles arabiensis. Furthermore, the antimicrobial properties of compounds CMRN1 - CMRN7 were evaluated by assessing the bacterial and fungicidal activities using the disc diffusion method. The anti-inflammatory properties were evaluated using the 5-lipoxygenase kit assay. The evaluation of the safe use of the compounds was determined using the Brine shrimp lethal test. The potential carcinogenic properties of the studied compounds was done using the Salmonella mutagenicity test. The anti-cancer property of the studied compounds was evaluated against UACC62 (Melanoma), MCF-7 (Breast cancer), and PBMC (Peripheral blood mononuclear) cell lines using of MTT assay. The apoptotic potential of the synthesized coumarin was evaluated against UACC62 (Melanoma) cell by assessing their morphological changes, membrane change, mitochondria membrane potential, and caspase-3 activity using the Annexin V-PI staining, JC-1, caspase-3 enzyme kits, respectively, on flow cytometer. The results were compared to a known anti-cancer drug, doxorubicin. The results showed that compounds CMRN1, CMRN2, CMRN4, CMRN5 and CMRN7 exerted 100% larval mortality within 24 h of exposure. All halogenated coumarins reversibly knocked down adult mosquitoes but did not kill them after 24 h of exposure. Furthermore, the adulticidal activity of the compounds was considered only mild to moderate. The antimicrobial activity of the synthetized coumarins CMRN1 - CMRN7 were assessed against E. coli, K. pneumoniae, S. marcescens, S. faecalis, B. cereus, B. coagulans, B. stearothermophilus, C. freundii, S. aureus and M. luteus bacteria and three yeast cultures, C. albicans, C. utilis, S. cerevisiae as well as two fungal species, A. flavus and A. niger. Compounds CMRN1 and CMRN2 showed bacterial growth inhibition for all the tested species except K. pneumonia and B. stearothermophilus. Compounds CMRN4 and CMRN7 showed moderate bacterial inhibition against B. cereus, M. luteus and S. aureus. The anti-inflammatory activity of the coumarins analogues showed that 1 mg/mL of the compounds CMRN1, CMRN2, CMRN4 and CMRN5 displayed moderate anti-inflammatory activity when compared to the positive control, 15-lapoxygenase. The cytotoxicity results of the studied synthetized coumarins displayed selective activity towards the cancer cell lines used in this study. Our studies showed that CMRN1, CMRN2, CMRN4, and CMRN5 had significant cytotoxity effect against UACC-62 (Melanoma) and MCF-7 ( Breast) cancer cells with an inhibitory concentration (IC50) which displayed significant cytotoxicity effect, in particular CMRN4 and CMRN5. These compounds CMRN1- CMRN7 showed no toxicity effect against PBMCs cell line. The mechanism of cell death, that is, necrosis or apoptosis induced by the coumarins was investigated against UACC-62 (Melanoma). We found that CMRN1, CMRN2, CMRN4, CMRN5 induced morphological changes, characteristic of apoptosis . Annexin V kit showed that CMRN1, CMRN2 and CMRN5 showed early apopotosis and late apoptosis was particularly higher for compound CMRN4. The disruption of the mitochondria membrane was noticed to be greater in CMRN1 and CMRN5 when compared to the positive control doxorubicin. Compound CMRN4 produced high levels of caspase-3 positive compared to the control. The coumarin compounds showed no mutagenicity and were also found to be non-toxic to brine shrimps. In conclusion, compounds CMRN1, CMRN2, CMRN4, CMRN5 and CMRN7 are potential larvicidal agents because they exhibited close to 100% activity within 24 h. Furthermore, the anti-cancer efficiency of compounds CMRN1, CMRN2, CMRN4, and CMRN5, is enough qualification for them to be optimized for increase anticancer potency.

scholarly journals Anticancer, Anti-Inflammatory, and Analgesic Activities of Synthesized 2-(Substituted phenoxy) Acetamide Derivatives

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Priyanka Rani ◽  
Dilipkumar Pal ◽  
Rahul Rama Hegde ◽  
Syed Riaz Hashim
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Therapeutic Agent ◽  
Inflammatory Activity ◽  
Substituted Phenols ◽  
New Chemical Entities ◽  
Analgesic Agents ◽  
Anti Inflammatory ◽  
Analgesic Activities ◽  
Mcf 7

The aphorism was to develop new chemical entities as potential anticancer, anti-inflammatory, and analgesic agents. The Leuckart synthetic pathway was utilized in development of novel series of 2-(substituted phenoxy)-N-(1-phenylethyl)acetamide derivatives. The compounds containing 1-phenylethylamine as basic moiety attached to substituted phenols were assessed for their anticancer activity against MCF-7 (breast cancer), SK-N-SH (neuroblastoma), anti-inflammatory activity, and analgesic activity. These investigations revealed that synthesized products3a–jwith halogens on the aromatic ring favors as the anticancer and anti-inflammatory activity. Among all, compound3cN-(1-(4-chlorophenyl)ethyl)-2-(4-nitrophenoxy)acetamide exhibited anticancer, anti-inflammatory, and analgesic activities. In conclusion,3cmay have potential to be developed into a therapeutic agent.

Design, synthesis, anticancer activity and mechanism studies of novel 2-amino-4-aryl-pyrimidine derivatives of ursolic acid

2022 ◽  
Author(s):  
Wen-Yan Wang ◽  
Zihui Yang ◽  
A-Liang Li ◽  
Qing-Song Liu ◽  
Yue Sun ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Ursolic Acid ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Pyrimidine Derivatives ◽  
Design Synthesis ◽  
Derivatives Of ◽  
Mcf 7

A series of novel 2-amino-4-aryl-pyrimidine derivatives of ursolic acid were designed, synthesized, and evaluated for their anticancer activities against four cancer cell lines (MCF-7, HeLa, HepG2, and A549) and a...

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.

(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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