Development of 2-oindolin-3-ylidene-indole-3-carbohydrazide derivatives as novel apoptotic and anti-proliferative agents towards colorectal cancer cells

Wagdy M. Eldehna; Mahmoud F. Abo-Ashour; Tarfah Al-Warhi; Sara T. Al-Rashood; Amal Alharbi; Rezk R. Ayyad; Khayal Al-Khayal; Maha Abdulla; Hatem A. Abdel-Aziz; Rehan Ahmad; Radwan El-Haggar

doi:10.1080/14756366.2020.1862100

References41

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Potent inhibitors of SARS-CoV-2 3C-like protease derived from N-substituted isatin compounds.

Nov 15, 2020·European Journal of Medicinal Chemistry6.51

#1Pei Liu (PKU: Peking University)H-Index: 4

#2Hongbo Liu (PKU: Peking University)H-Index: 6

Last. Luhua Lai (PKU: Peking University)H-Index: 60

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Abstract SARS-CoV-2 3C-like protease is the main protease of SARS-CoV-2 and has been considered as one of the key targets for drug discovery against COVID-19. We identified several N-substituted isatin compounds as potent SARS-CoV-2 3C-like protease inhibitors. The three most potent compounds inhibit SARS-CoV-2 3C-like protease with IC50’s of 45 nM, 47 nM and 53 nM, respectively. Our study indicates that N-substituted isatin compounds have the potential to be developed as broad-spectrum anti-cor...more

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Novel [(N-alkyl-3-indolylmethylene)hydrazono]oxindoles arrest cell cycle and induce cell apoptosis by inhibiting CDK2 and Bcl-2: synthesis, biological evaluation and in silico studies.

Jun 11, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry5.05

#1Tarfah Al-WarhiH-Index: 10

#2Mahmoud F. Abo-Ashour (Egyptian Russian University)H-Index: 10

Last. Hatem A. Abdel-AzizH-Index: 36

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As a continuation for our previous work, a novel set of N-alkylindole-isatin conjugates (7, 8a-c, 9 and 10a-e) is here designed and synthesised with the prime aim to develop more efficient isatin-based antitumor candidates. Utilising the SAR outputs from the previous study, our design here is based on appending four alkyl groups with different length (ethyl and n-propyl), bulkiness (iso-propyl) and unsaturation (allyl) on N-1 of indole motif, with subsequent conjugation with different N-unsubsti...more

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Synthesis, Biological Evaluation and In Silico Studies of Certain Oxindole-Indole Conjugates as Anticancer CDK Inhibitors.

Apr 27, 2020·Molecules4.41

#1Tarfah Al-Warhi (Princess Nora bint Abdul Rahman University)H-Index: 10

#2Ahmed M. El Kerdawy (Cairo University)H-Index: 14

Last. Ghada H. Al-AnsaryH-Index: 11

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On account of their overexpression in a wide range of human malignancies, cyclin-dependent kinases (CDKs) are among the most validated cancer targets, and their inhibition has been featured as a valuable strategy for anticancer drug discovery. In this study, a hybrid pharmacophore approach was adopted to develop two series of oxindole–indole conjugates (6a–i and 9a–f) and carbocycle–indole conjugates (11a,b) as efficient antitumor agents with potential inhibitory action toward CDK4. All oxindole...more

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Recent advances in isatin hybrids as potential anticancer agents

Jan 21, 2020·Archiv Der Pharmazie3.75

#1Zhen DingH-Index: 1

#2Minfeng Zhou (Shaoxing University)H-Index: 1

Last. Cheng ZengH-Index: 1

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The isatin framework is a useful template for the development of novel anticancer agents. This is exemplified by the fact that several isatin-based anticancer agents, such as semaxanib, sunitinib, nintedanib, and hesperadin, are already in use or under clinical trials for the treatment of diverse kinds of cancers. Isatin-based hybrids could be obtained by incorporating other anticancer pharmacophores into the isatin skeleton and they have the potential to overcome drug resistance with reduced si...more

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3-Hydrazinoisatin-based benzenesulfonamides as novel carbonic anhydrase inhibitors endowed with anticancer activity: Synthesis, in vitro biological evaluation and in silico insights

Dec 15, 2019·European Journal of Medicinal Chemistry6.51

#1Mahmoud F. Abo-Ashour (Egyptian Russian University)H-Index: 10

#2Wagdy M. Eldehna (Kafrelsheikh University)H-Index: 26

Last. Claudiu T. Supuran (UniFI: University of Florence)H-Index: 155

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Abstract Herein we describe the design and synthesis of two series of sulfonamides featuring N-unsubstituted (4a-c) or N-substituted (7a-o) isatin moieties (as tails) connected to benzenesulfonamide moiety via a hydrazine linker. All the prepared sulfonamides (4a-c and 7a-o) showed potent inhibitory activities toward transmembrane tumor-associated human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, IX and XII with KI range (8.3–65.4 nM) and (11.9–72.9 nM), respectively. Furthermore, six sul...more

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Induction of ROS‑mediated cell death and activation of the JNK pathway by a sulfonamide derivative.

Oct 1, 2019·International Journal of Molecular Medicine4.10

#1Rehan Ahmad (KSU: King Saud University)H-Index: 31

#2Mansoor‑Ali Vaali‑Mohammed (KSU: King Saud University)H-Index: 1

Last. Maha Abdulla (KSU: King Saud University)H-Index: 8

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: The emergence of colorectal cancer in developed nations can be attributed to dietary habits, smoking, a sedentary lifestyle and obesity. Several treatment regimens are available for primary and metastatic colorectal cancer; however, these treatment options have had limited impact on cure and disease‑free survival, and novel agents need to be developed for treating colorectal cancer. Thus, the objective of this study was to explore the anticancer mechanism of a benzo(1,3)dioxol‑based derivative...more

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Systematic Review on Cytotoxic and Anticancer Potential of N -Substituted Isatins as Novel Class of Compounds Useful in Multidrug-Resistant Cancer Therapy: In Silico and In Vitro Analysis

May 9, 2019·Topics in Current Chemistry9.06

#1Alpana K. Gupta (ICMR: Indian Council of Medical Research)H-Index: 8

#2Sonam Tulsyan (ICMR: Indian Council of Medical Research)H-Index: 5

Last. Ravi Mehrotra (ICMR: Indian Council of Medical Research)H-Index: 51

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As the emergence of resistance to clinical cancer treatments poses a significant problem in cancer management, there is a constant need to explore novel anticancer agents which have the ability to overcome multidrug resistance (MDR) mechanisms. The search for the development of novel isatin-based antitumor agents accelerated after the approval by the Food and Drug Administration (FDA) of sunitinib malate, a C-3 isatin derivative, as a multitargeted receptor tyrosine kinase inhibitor. However, it...more

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Type IIA - Type IIB protein tyrosine kinase inhibitors hybridization as an efficient approach for potent multikinase inhibitor development: Design, synthesis, anti-proliferative activity, multikinase inhibitory activity and molecular modeling of novel indolinone-based ureides and amides.

Feb 1, 2019·European Journal of Medicinal Chemistry6.51

#1Wagdy M. Eldehna (Kafrelsheikh University)H-Index: 26

#2Ahmed M. El Kerdawy (Cairo University)H-Index: 14

Last. Abeer E. MahmoudH-Index: 12

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Abstract Pursuing on our efforts regarding development of novel multikinase inhibitors, herein we report the design and synthesis of novel 2-indolinone-based ureides 6a-u and amides 10a-j. In this work we adopt a hybridization strategy between type IIA PTK inhibitor (sorafenib) and type IIB PTK inhibitors (sunitinib and nintedanib). This was implemented via linking the indolinone core, in both sunitinib and nintedanib, which is well-fitted in the hinge region in the kinase domain front cleft and...more

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Aryl hydrocarbon receptor pathway participates in myocardial ischemia reperfusion injury by regulating mitochondrial apoptosis.

Feb 1, 2019·Medical Hypotheses1.54

#1Beibei Wang (HUST: Huazhong University of Science and Technology)H-Index: 1

#2Aijun Xu (HUST: Huazhong University of Science and Technology)H-Index: 1

Abstract Reducing ischemia reperfusion (I/R) injury has been a major challenge in the treatment of cardiovascular disease. It is widely accepted that mitochondrial apoptosis is an important link in myocardial infarction induced by I/R damage. Studies suggested that aryl hydrocarbon receptor (AhR) pathway plays an important role in the development and function of the cardiovascular system and regulating the mitochondrial homeostasis. AhR played a critical role in regulating mitochondrial homeosta...more

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Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: Design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitors and antitumor agents.

Jan 15, 2019·European Journal of Medicinal Chemistry6.51

#1Wagdy M. Eldehna (Kafrelsheikh University)H-Index: 26

#2Mahmoud F. Abo-Ashour (Egyptian Russian University)H-Index: 10

Last. Claudiu T. Supuran (UniFI: University of Florence)H-Index: 155

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Abstract Herein we report the design and synthesis of novel N-substituted isatins-SLC-0111 hybrids (6a-f and 9a-l). A structural extension approach was adopted via N-alkylation and N-benzylation of isatin moiety to enhance the tail hydrophobic interactions within the carbonic anhydrase (CA) IX active site. Thereafter, a hybrid pharmacophore approach was utilized via merging the pharmacophoric elements of isatin and SLC-0111 in a single chemical framework. As planned, a substantial improvement of...more

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