Mannich Bases: Centrality in Cytotoxic Drug Design

2021 ◽  
Vol 18 ◽  
Author(s):  
Neha V. Bhilare ◽  
Vinayak S. Marulkar ◽  
Pramodkumar J. Shirote ◽  
Shailaja A. Dombe ◽  
Vilas J. Pise ◽  
...  
Keyword(s):  
Drug Design ◽  
Drug Development ◽  
Cell Lines ◽  
Mannich Bases ◽  
Cytotoxic Agents ◽  
Structure Activity ◽  
Anti Cancer ◽  
Methods Of Synthesis ◽  
Future Drug ◽  
Clinical Conditions

: Mannich bases identified by Professor Carl Mannich have been the most extensively explored scaffolds for more than 100 years now. The versatile biological roles that they play have promoted their applications in many clinical conditions. The present review highlights the application of Mannich bases as cytotoxic agents, categorizing them into synthetic, semisynthetic and prodrugs classes and gives an exhaustive account of the work reported in the last two decades. The methods of synthesis of these cytotoxic agents, their anti-cancer potential in various cell lines and promising leads for future drug development have also been discussed. Structure-activity relationships along with the targets on which these cytotoxic Mannich bases act have been included as well.

The Design and Synthesis of Novel Phenothiazine Derivatives as Potential Cytotoxic Agents

2019 ◽  
Vol 17 (1) ◽  
pp. 57-67
Author(s):  
Yepeng Luan ◽  
Jinyi Liu ◽  
Jianjun Gao ◽  
Jinhua Wang
Keyword(s):  
Cell Lines ◽  
High Efficiency ◽  
Human Cancer ◽  
Human Tumor ◽  
Cytotoxic Agents ◽  
Cancer Drug ◽  
Human Cancer Cell Lines ◽  
Incidence And Mortality ◽  
Anti Cancer

Background: Cancer incidence and mortality have been increasing and cancer is still the leading cause of death all over the world. Despite the enormous progress in cancer treatment, many patients died of ineffective chemotherapy and drug resistance. Therefore, the design and development of anti-cancer drugs with high efficiency and low toxicity is still one of the most challenging tasks. Tricyclic heterocycles, such as phenothiazine, are always important sources of scaffolds for anti-cancer drug discovery. Methods: In this work, ten new urea-containing derivatives of phenothiazine coupled with different kinds of amine motifs at the endpoint through a three carbon long spacer were designed and synthesized. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR and HRMS. All the synthesized compounds were tested for their antitumor activity in vitro against the proliferation of PC-3 cells, and the compounds with best potency entered further cytotoxicity evaluations against other 22 human tumor cell lines. Mechanism was also studied. Results: From all data, it showed that among all 10 target compounds, TTi-2 showed the best effect in inhibiting the proliferation of 23 human cancer cell lines while TTi-2 without obvious inhibitory effect on normal cell. Furthermore, our results also showed that TTi-2 could inhibit migration, invasion and colony formation of MDA-MB-231 cells. Finally, TTi-2 can induce arrest of cell cycle at G0/G1 phase and cell apoptosis by activating the caspase 3 activity. Conclusion: All these results suggested that TTi-2 might be used as a promising lead compound for anticancer drug development.

Nano-SnCl4/SiO2 as a Catalyst for One-Pot Synthesis of Substituted 1H-Pyrazoles as Antifungal and Cytotoxic Agents

2020 ◽  
Vol 17 (6) ◽  
pp. 459-465
Author(s):  
Soghra Khabnadideh ◽  
Zeinab Faghih ◽  
Leila Zamani ◽  
Kamiar Zomorodian ◽  
Bi Bi Fatemeh Mirjalili ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cancer ◽  
Antimicrobial Activities ◽  
Cytotoxic Agents ◽  
Cytotoxic Activities ◽  
Pyrazole Derivatives ◽  
One Pot ◽  
Human Cancer Cell Lines ◽  
Cancerous Cell ◽  
Anti Cancer

A simple and efficient method was developed for the synthesis of pyrazole derivatives via a one-pot reaction of 1,3-diketone and substituted hydrazines in the presence of nano-SnCl4/SiO2 as a mild catalyst. A series of some pyrazole derivatives (P1-P11) was synthesized and evaluated as antifungal and anti-cancer agents. Compounds P10 and P11 were demonstrated. The antimicrobial activities of the synthetic compounds showed that compounds P10 and P11 most excellently inhibited the growth of dermatophytes or Aspergillus species, respectively. Therefore, the cytotoxic activities of these compounds on two human cancer cell lines, A549 (lung cancer) and MCF-7 (breast cancer) were further assessed. Hence, results demonstrated that beside antifungal activity, P10 had also desirable cytotoxic effect on investigated cancerous cell lines, even higher than cisplatin.

The Uses of Dimedone for the Synthesis of Thiophene, Thiazole and Annulated Derivatives with Antitumor, Pim-1 Kinase Inhibitions, PAINS Evaluations and Molecular Docking

2021 ◽  
Vol 21 ◽  
Author(s):  
Wagnat W. Wardakhan ◽  
Amira M. Elmetwally ◽  
Abeer A. Mohamed ◽  
Rafat M. Mohareb
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tyrosine Kinases ◽  
Heterocyclic Compounds ◽  
Cancer Cell Lines ◽  
Strong Impact ◽  
Structure Activity ◽  
Anti Cancer ◽  
Target Molecules

Background: Dimedone is considered as one of the most important class of compounds belonging to cyclohexan-1,3-dione. Such group of compounds were considered as precursors for many pharmaceutically active heterocyclic compounds. Objective: The target molecules through this work were synthesized from arylhydrazones of dimedone with different substituent’s enhancing study of their structure activity relationship. Methods: Arylhydrazones of dimedones were subjected to a series of heterocyclization reactions affording annulated compounds. The antiproliferative activities of the synthesized molecules were evaluated against six cancer cell lines. In addition, inhibitions toward tyrosine kinases, Pim-1 kinases and PAINS of the most active compounds were also studied. c-Met enzymatic inhibitions and molecular docking studied were carried for three compounds. Results: Anti-cancer evaluations together with tyrosine and Pim-1 kinases of most of the synthesized compounds were carried out through this work. The study revealed that changing of substituent had a strong impact on the activity of themolecule. Conclusion: Many of the synthesized compounds exhibited high inhibitions toward the six cancer cell lines and this will encourage further work through the synthesis of target molecule with the same ring systems. The three compounds 7b, 8c and 12b that revealed excellent inhibitions were tested against c-Met kinase and their molecular modelling was expressed.

Triarylpyrazole Derivatives as Potent Cytotoxic Agents; Synthesis and Bioactivity Evaluation “Pyrazole Derivatives as Anticancer Agent”

Drug Research ◽  
2021 ◽  
Author(s):  
Bilqees Sameem ◽  
Ebrahim Saeedian Moghadam ◽  
Majid Darabi ◽  
Zahra Shahsavari ◽  
Mohsen Amini
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Carcinoma Cells ◽  
Cytotoxic Agents ◽  
Cancer Drug ◽  
Pyrazole Derivatives ◽  
Anti Cancer ◽  
Ht 29

Abstract Background During the last recent years, several anti-cancer agents were introduced for the treatment of diverse kinds of cancer. Despite their potential in the treatment of cancer, drug resistance and adverse toxicity such as peripheral neuropathy are some of the negative criteria of anti-cancer agents and for this reason, the design and synthesis of new anti-cancer agents are important. Objective Design, synthesis, and anticancer activity evaluation of some pyrazole derivatives. Methods A series of Target compounds were prepared using multistep synthesis. Their cytotoxic activity against three different human cancer cell lines namely human colon carcinoma cells (HT-29), epithelial carcinoma cells (U-87MG), pancreatic cancerous cells (Panc-1) as well as AGO1522 normal cell line using in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was investigated. Results 1,3-Diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole and 1,3-Diaryl-5-(3,4,5-trimethoxyphenyl)- 1H-pyrazole were synthesized in good yields and their structure and purity were confirmed using 1H-NMR, 13C-NMR, and elemental analysis. Generally, the synthesized scaffolds exhibited good cytotoxicity against cancerous cell lines in comparison to the reference standard, paclitaxel. Compounds 3a and 3c, in Annexin V/ PI staining assay, exerted remarkable activity in apoptosis induction in HT-29 cell lines. Both of them also led to cell cycle arrest in the sub-G1 phase which is inconsistent with the results of apoptosis assay. Conclusion Concerning obtained results, it is interesting to synthesis more pyrazole derivatives as anticancer agents.

Utility of Certain 2-Furanone Derivatives for Synthesis of Different Heterocyclic Compounds and Testing their Anti-cancer Activity

2021 ◽  
Vol 17 ◽  
Author(s):  
Rania Helmy Abd El-Hameed ◽  
Hend Medhat El-Shanbaky ◽  
Mosaad Sayed Mohamed
Keyword(s):  
Cell Lines ◽  
Heterocyclic Compounds ◽  
Development Process ◽  
Biological Activities ◽  
Biologically Active ◽  
Cytotoxic Agents ◽  
Inhibition Activity ◽  
Small Cell Lung ◽  
Anti Cancer ◽  
Hct 116

Background: 2-Furanones attracted great attention due to their biological activities. They also have the ability to convert to several biologically active heterocyclic and non-heterocyclic compounds, especially as anti-cancer agents. Objectives: This research aims to assist in the development process of novel cytotoxic agents through synthesizing certain 2-furanone derivatives, using them as starting materials for the preparation of novel heterocyclic and non-heterocyclic compounds, and then testing the synthesized derivatives for their anti-cancer activities. Methods: All the newly synthesized compounds were fully characterized by elemental analysis, IR, Mass, and 1H-NMR spectroscopy. 18 synthesized compounds were selected by National Cancer Institute (NCI) for testing against 60 cell lines, and the active compound was tested as MAPK14 and VEGFR2-inhibitor using Staurosporine as standard. Results: Compound 3a showed higher activity against several cell lines, including leukemia (SR), Non-Small Cell Lung Cancer (NCI-H460), colon cancer (HCT-116), ovarian cancer (OVCAR-4), renal cancer (786-0, ACHN and UO-31), and finally breast cancer (T-47D). It also had better inhibition activity against MAPK14 than the used reference. Conclusion: Compound 3a has promising anti-cancer activities compared to the used standards and may need further modifications and investigations.

SYNTHESIS OF 1,3-THIAZOLE DERIVATIVES

INDIAN DRUGS ◽  
2021 ◽  
Vol 58 (01) ◽  
pp. 7-19
Author(s):  
Rebaz Omar ◽  
◽  
Pelin Koparir ◽  
Metin Koparir ◽  
Keyword(s):  
Nitrogen Atom ◽  
Drug Design ◽  
Drug Development ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Thiazole Derivatives ◽  
Anti Cancer ◽  
Drug Synthesis ◽  
Anti Oxidant ◽  
Anti Hiv

Many heterocyclic compounds containing nitrogen atom are used in drug development. Thiazole is one of the most important heterocyclic compounds in drug design, which contains sulfur and nitrogen atom. Different site reactions in thiazole compounds extend to new drug synthesis and plays an important role in medicinal chemistry. Thiazole and derivatives are found to possess widely biological activities such as anti-inflammatory, anti-diabetic, anti-microbial, anti-cancer, anti-consulsant, anti-HIV, anti-hypertensive, anti-Alzheimer, anti-oxidant and anthelmintic. The aim of this review is to corroborate procedures which are available for the synthesis 1,3-thiazole derivatives

scholarly journals Quinazoline pharmacophore in therapeutic medicine

2016 ◽  
Vol 11 (3) ◽  
pp. 716 ◽  
Author(s):  
Olayinka Oyewale Ajani ◽  
Damilola Victoria Aderohunmu ◽  
Ejike Nzube Umeokoro ◽  
Ayodele Ojo Olomieja
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Drug Design ◽  
Infectious Diseases ◽  
Drug Development ◽  
Molecular Targets ◽  
Beneficial Role ◽  
Future Drug ◽  
Broad Overview

<p>This present study comprehensively expatiates the functionalized utilization of quinazoline scaffolds in drug development and furnishes latest updates in pharmacological appositeness of its derivatives in order to reveal novel pathways for therapeutic targets. It traverses numerous biological potentials of quinazoline in the contemporary time to allow researchers’ unhindered access to the beneficial role of quinazoline in fighting infectious diseases for future drug discovery. This work provides broad overview of medicinal survey of quinazoline chemistry valuable in the discovery of more efficient clinical trials and to summarize the most promising molecular targets for drug design.  </p>

scholarly journals A Novel Drug Design Strategy: An Inspiration from Encaging Tumor by Metallofullerenol Gd@C82(OH)22

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2387
Author(s):  
Jinxia Li ◽  
Linlin Chen ◽  
Liang Yan ◽  
Zhanjun Gu ◽  
Zhaofang Chen ◽  
...  
Keyword(s):  
Drug Design ◽  
Surface Characteristics ◽  
Great Promise ◽  
Anti Cancer ◽  
Future Drug ◽  
Tumor Growth And Metastasis ◽  
Reduced Toxicity ◽  
Dynamic Key ◽  
Novel Drug ◽  
Shed Light

Cancer remains a major threat to human health worldwide. Cytotoxicity has imposed restrictions on the conventional cytotoxic drug-based chemotherapy. The rapidly-developing nanomedicine has shown great promise in revolutionizing chemotherapy with improved efficiency and reduced toxicity. Gd@C82(OH)22, a novel endohedral metallofullerenol, was first reported by our research group to suppress tumor growth and metastasis efficiently without obvious toxicity. Gd@C82(OH)22 imprisons tumors by facilitating the formation of surrounding fibrous layers which is different from chemotherapeutics that poison tumor cells. In this review, the authors first reported the antineoplastic activity of metallofullerenol Gd@C82(OH)22 followed by further discussions on its new anti-cancer molecular mechanism—tumor encaging. On this basis, the unparalleled advantages of nanomedicine in the future drug design are discussed. The unique interaction modes of Gd@C82(OH)22 with specific targeted biomolecules may shed light on a new avenue for drug design. Depending on the surface characteristics of target biomolecules, nanomedicine, just like a transformable and dynamic key, can self-assemble into suitable shapes to match several locks for the thermodynamic stability, suggesting the target-tailoring ability of nanomedicine.

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