Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents

Prostate cancer is one of the leading causes of death in men all over the world. Treatment options such as androgen ablation therapy and cytotoxic agents have many undesirable side effects, narrow therapeutic windows, or other limitations. In this research, we have explored the effects of paeonol on prostate cancer and its mechanism of action. Our results have shown that paeonol reduced the viability of prostate cancer cells in a dose-dependent manner. The wound-healing assay, a surrogate marker of tumor metastasis, showed that the relative wound width of 10 µM group was less than that of 50 µM paeonol-treated cells. Besides, the results of the transwell assay also showed that the number of migrated cells was significantly lower after treatment with 50 µM paeonol compared to the 10 µM group. The Western blot results showed that paeonol treatment induced a decrease in the mesenchymal markers (vimentin and N-cadherin), while the epithelial marker (E-cadherin) increased in a dose-dependent manner suggesting that paeonol effectively inhibits the epithelial-mesenchymal transformation in PC3 cells. Furthermore, the expression of STAT3 and p-STAT3 was also decreased after paeonol treatment, which indicated that the STAT3 signaling pathway was inhibited by paeonol. To conclude, the results summarized in this paper suggest that paeonol could be a potential candidate in the treatment of prostate cancer.

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Bioactive Secondary Metabolites from Endophytic Fungi

Current Medicinal Chemistry ◽

10.2174/0929867326666190916144709 ◽

2020 ◽

Vol 27 (11) ◽

pp. 1836-1854 ◽

Cited By ~ 5

Author(s):

Elena Ancheeva ◽

Georgios Daletos ◽

Peter Proksch

Keyword(s):

Secondary Metabolites ◽

Endophytic Fungi ◽

Host Plants ◽

Biological Activities ◽

Cytotoxic Agents ◽

Special Focus ◽

Plant Metabolites ◽

Direct Production ◽

Bioactive Secondary Metabolites ◽

Fungal Genes

Background: Endophytes represent a complex community of microorganisms colonizing asymptomatically internal tissues of higher plants. Several reports have shown that endophytes enhance the fitness of their host plants by direct production of bioactive secondary metabolites, which are involved in protecting the host against herbivores and pathogenic microbes. In addition, it is increasingly apparent that endophytes are able to biosynthesize medicinally important “phytochemicals”, originally believed to be produced only by their host plants. Objective: The present review provides an overview of secondary metabolites from endophytic fungi with pronounced biological activities covering the literature between 2010 and 2017. Special focus is given on studies aiming at exploration of the mode of action of these metabolites towards the discovery of leads from endophytic fungi. Moreover, this review critically evaluates the potential of endophytic fungi as alternative sources of bioactive “plant metabolites”. Results: Over the past few years, several promising lead structures from endophytic fungi have been described in the literature. In this review, 65 metabolites are outlined with pronounced biological activities, primarily as antimicrobial and cytotoxic agents. Some of these metabolites have shown to be highly selective or to possess novel mechanisms of action, which hold great promises as potential drug candidates. Conclusion: Endophytes represent an inexhaustible reservoir of pharmacologically important compounds. Moreover, endophytic fungi could be exploited for the sustainable production of bioactive “plant metabolites” in the future. Towards this aim, further insights into the dynamic endophyte - host plant interactions and origin of endophytic fungal genes would be of utmost importance.

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Synthesis and Evaluation of Aromatic Surfactants as Potential Antibacterial and Cytotoxic Agents

Letters in Organic Chemistry ◽

10.2174/1570178615666181023151308 ◽

2019 ◽

Vol 16 (6) ◽

pp. 478-484

Author(s):

Kenia Barrantes ◽

Mary Fuentes ◽

Luz Chacón ◽

Rosario Achí ◽

Jorge Granados-Zuñiga ◽

...

Keyword(s):

Antibacterial Activity ◽

Hela Cells ◽

Cytotoxic Agents ◽

Cytotoxic Activities ◽

Hydroxybenzoic Acid ◽

Derivatives Of

Two ether and one ester derivatives of the 4-nitro-3-hydroxybenzoic acid were synthesized and characterized. The in vitro antimicrobial and cytotoxic activities of the three novel compounds were also evaluated. The aromatic derivatives showed antibacterial activity against one of the four microorganisms tested and two compounds (C8 and NOBA) had a lower IC50 in HeLa cells.

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Synthesis of Sulfur Containing Colchicine Derivatives and their Biological Evaluation as Cytotoxic Agents

Letters in Drug Design & Discovery ◽

10.2174/15701808113106660086 ◽

2014 ◽

Vol 11 (3) ◽

pp. 279-289 ◽

Cited By ~ 6

Author(s):

Joanna Kurek ◽

Wladyslaw Boczon ◽

Krzysztof Myszkowski ◽

Marek Murias ◽

Teresa Borowiak ◽

...

Keyword(s):

Biological Evaluation ◽

Cytotoxic Agents ◽

Colchicine Derivatives ◽

Sulfur Containing

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p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies

Letters in Drug Design & Discovery ◽

10.2174/1570180816666181128112249 ◽

2020 ◽

Vol 17 (2) ◽

pp. 169-183 ◽

Cited By ~ 1

Author(s):

İrem Bozbey ◽

Suat Sari ◽

Emine Şalva ◽

Didem Kart ◽

Arzu Karakurt

Keyword(s):

Molecular Modeling ◽

Neuroblastoma Cell ◽

Neuroblastoma Cells ◽

Cytotoxic Agents ◽

Human Neuroblastoma Cell ◽

Human Neuroblastoma ◽

Modeling Studies ◽

Broth Microdilution Method ◽

Molecular Modeling Studies

Background: Azole antifungals are among the first-line drugs clinically used for the treatment of systemic candidiasis, a deadly type of fungal infection that threatens mostly immunecompromised and hospitalized patients. Some azole derivatives were also reported to have antiproliferative effects on cancer cells. Objective: In this study, 1-(4-trifluoromethylphenyl)-2-(1H-imidazol-1-yl)ethanone (3), its oxime (4), and a series of its novel oxime ester derivatives (5a-v) were synthesized and tested for their in vitro antimicrobial activities against certain ATCC standard strains of Candida sp. fungi and bacteria. The compounds were also tested for their cytotoxic effects against mouse fibroblast and human neuroblastoma cell lines. Molecular modeling studies were performed to provide insights into their possible mechanisms for antifungal and antibacterial actions. Methods: The compounds were synthesized by the reaction of various oximes with acyl chlorides. Antimicrobial activity of the compounds was determined according to the broth microdilution method. For the determination of cytotoxic effect, we used MTS assay. Molecular docking and QM/MM studies were performed to predict the binding mechanisms of the active compounds in the catalytic site of C. albicans CYP51 (CACYP51) and S. aureus flavohemoglobin (SAFH), the latter of which was created via homology modeling. Results: 5d, 5l, and 5t showed moderate antifungal activity against C. albicans, while 3, 5c, and 5r showed significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Most of the compounds showed approximately 40-50% inhibition against the human neuroblastoma cells at 100 µM. In this line, 3 was the most potent with an IC50 value of 82.18 μM followed by 5a, 5o, and 5t. 3 and 5a were highly selective to the neuroblastoma cells. Molecular modelling results supported the hypothesis that our compounds were inhibitors of CAYP51 and SAFH. Conclusion: This study supports that oxime ester derivatives may be used for the development of new antimicrobial and cytotoxic agents.

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Synthesis and Biological Evaluation of Novel Osthol Derivatives as Potent Cytotoxic Agents

Medicinal Chemistry ◽

10.2174/1573406414666180911161047 ◽

2019 ◽

Vol 15 (2) ◽

pp. 138-149

Author(s):

Saleem Farooq ◽

Javid A. Banday ◽

Aashiq Hussain ◽

Momina Nazir ◽

Mushtaq A. Qurishi ◽

...

Keyword(s):

Cancer Cells ◽

Natural Product ◽

Cancer Therapeutics ◽

Inhibitory Effect ◽

Biological Evaluation ◽

Negative Control ◽

Normal Breast ◽

Cytotoxic Agents ◽

Breast Epithelial Cell ◽

Exciting Field

Background: Natural product, osthol has been found to have important biological and pharmacological roles particularly having inhibitory effect on multiple types of cancer. Objective: The unmet needs in cancer therapeutics make its derivatization an important and exciting field of research. Keeping this in view, a whole new series of diverse analogues of osthol (1) were synthesized. Method: All the newly synthesized compounds were made through modification in the lactone ring as well as in the side chain of the osthol molecule and were subjected to anti-proliferative screening through 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) against four different human cancers of diverse origins viz. Colon (Colo-205), lung (A549), Leukemia (THP- 1) and breast (MCF-7) including SV40 transformed normal breast epithelial cell (fR-2). Results: Interestingly, among the tested molecules, most of the analogs displayed better antiproliferative activity than the parent Osthol 1. However, among all the tested analogs, compound 28 exhibited the best results against leukemia (THP1) cell line with IC50 of 5µM.Compound 28 induced potent apoptotic effects and G1 phase arrest in leukemia cancer cells (THP1). The population of apoptotic cells increased from 13.8% in negative control to 26.9% at 8μM concentration of 28. Compound 28 also induced a remarkable decrease in mitochondrial membrane potential (ΛΨm) leading to apoptosis of the cancer cells. Conclusion: A novel series of molecules derived from natural product osthol were synthesized, wherein compound 28 was found to be most effective against leukemia and with 10 fold less toxicity against normal cells. The compound induced cancer inhibition mainly through apoptosis and thus has a potential in cancer therapeutics.

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