Synthesis and biological evaluation of certain hydrazonoindolin-2-one derivatives as new potent anti-proliferative agents

Eldehna, Wagdy M.; Al-Wabli, Reem I.; Almutairi, Maha S.; Keeton, Adam B.; Piazza, Gary A.; Abdel‐Aziz, Hatem A.; Attia, Mohamed I.

doi:10.1080/14756366.2018.1462802

Cited by 50 publications

(31 citation statements)

References 31 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cytotoxic activity of the active conjugates towards MDA-MB-231 cells ( 4c – e , 4g , 4l – n and 7a – d ) was examined against nontumorigenic human lung fibroblast cell line (WI-38) and human breast epithelial cell line (MCF-10A) to investigate the potential safety of the newly prepared conjugates towards the normal cells. Cultures derived from human fibrocystic mammary tissue (MCF-10A) are nontumorigenic and possess the features of primary cultures of breast tissue including dome formation [ 42 ]. The results were expressed as IC 50 values, and selectivity index was calculated ( Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Novel Thiazolidinone/Thiazolo[3,2-a]Benzimidazolone-Isatin Conjugates as Apoptotic Anti-proliferative Agents Towards Breast Cancer: One-Pot Synthesis and In Vitro Biological Evaluation

et al. 2018

View full text Add to dashboard Cite

In connection with our research program on the development of new isatin-based anticancer candidates, herein we report the synthesis of two novel series of thiazolidinone-isatin conjugates (4a–n) and thiazolo[3,2-a]benzimidazolone-isatin conjugates (7a–d), and in vitro evaluation of their antiproliferative activity towards two breast cancer cell lines; triple negative MDA-MB-231, and MCF-7. Compounds 4m and 7b emerged as the most active congeners against MDA-MB-231 cells (IC50 = 7.6 ± 0.5 and 13.2 ± 1.1 µM, respectively). Compounds 4m and 7b were able to provoke apoptosis in MDA-MB-231 cells, evidenced by the up-regulation of Bax and down-regulation of Bcl-2, besides boosting caspase-3 levels. Hybrid 4m induced a fourfold increase in the percentage of cells at Sub-G1, with concurrent arrest in G2-M phase by 2.5-folds. Furthermore, hybrid 4m resulted in a sixfold increase in the percentage of annexin V-FITC positive apoptotic MDA-MB-231 cells as compared with the control. Moreover, the cytotoxic activities of the active conjugates were assessed towards two nontumorigenic cell lines (breast MCF-10A and lung WI-38) where both conjugates 4m and 7b displayed mean tumor selectivity index: 9.6 and 13.9, respectively. Finally, several ADME descriptors were predicted for the active conjugates via a theoretical kinetic study.

show abstract

Section: Resultsmentioning

confidence: 99%

“…The cytotoxic activity of the active conjugates towards nontumorigenic human lung fibroblast cell line (WI-38) and human breast epithelial cell line (MCF-10A) was determined using Crystal violet (CV) cell cytotoxicity assay according to the previously published procedures [ 42 , 55 ].…”

Section: Methodsmentioning

confidence: 99%

Novel Thiazolidinone/Thiazolo[3,2-a]Benzimidazolone-Isatin Conjugates as Apoptotic Anti-proliferative Agents Towards Breast Cancer: One-Pot Synthesis and In Vitro Biological Evaluation

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The anticancer SAR of isatin–thiazole hybrids 22 (IC 50 : 1.16–15.32 μM, MTT assay) and 23 (IC 50 : 1.87–24.59 μM) against A549, ZR‐75, and HT‐29 cancer cell lines revealed that thiazole moiety was essential for the high activity and incorporation of halogen atoms into C‐5 position of isatin core could improve the activity. [ 79 ] Introduction of thiazolidinone fragments between isatin and thiazole motifs reduced the activity as evidenced by the fact that hybrids 24 were devoid of activity against a panel of 60 cancer cell lines. [ 80 ] The electron‐donating group at R 2 position was favorable to the activity for hybrids 22 , whereas either electron‐donating or electron‐withdrawing group at R 2 position was harmful to the activity for hybrids 23 .…”

Section: Isatin–coumarin Hybridsmentioning

confidence: 99%

“…The anticancer SAR of isatin–pyrazole hybrids 26 (IC 50 : 1.37–22.94 μM, MTT assay) against A549, ZR‐75, and HT‐29 cancer cell lines indicated that introduction of halogen atom into C‐5 position of isatin moiety could boost up the activity. [ 79 ] In particular, hybrid 26b (IC 50 : 1.37–2.75 μM) was not only 2.1–6.0‐fold more active than sunitinib (IC 50 : 5.87–10.14 μM) against A549, ZR‐75, and HT‐29 cancer cell lines, but also showed potential activity (IC 50 : 16 μM) against NCI‐H69AR multidrug‐resistant lung cancer cells which could express the human multidrug resistance‐associated protein 1 (ABCC1) efflux pump protein, highlighting the significance of exploring the isatin–pyrazole hybrids for fighting against both drug‐sensitive and drug‐resistant cancers. The isatin–pyrazole hybrids 27a,b (IC 50 : 30.41 and 29.69 μM, CCK‐8 assay) and 28 (IC 50 : 58.48 μM) were active against A549 cancer cells and the SAR proved that introduction of halogen atoms into C‐6 position of isatin moiety could improve the activity.…”

Section: Isatin–coumarin Hybridsmentioning

confidence: 99%

Recent advances in isatin hybrids as potential anticancer agents

Ding

Zhou

Zeng

2020

Archiv der Pharmazie

View full text Add to dashboard Cite

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 side effects. Thus, isatin‐based hybrids may provide attractive scaffolds for the development of novel anticancer agents. This review covers the recent advances of isatin‐based hybrids with anticancer activity, covering articles published between 2001 and 2019. The anticancer activities of these molecules and the structure–activity relationships are also discussed. The purpose of this review article is to set up the direction for the design and development of isatin‐based hybrids with high efficacy and low toxicity.

show abstract

“…Being abundant in nature, isatins have been found in fluids and tissues of mammals, in addition to natural products that are produced by a range of bacteria, plants, and invertebrates 10 . Isatin motif is a central privileged scaffold in a large number of bioactive natural and synthetic products that possess a spectrum of bioactivities such as antioxidant 11 and anticancer activities [12][13][14] . On the other hand, the natural spirooxindole alkaloids were first isolated from plants of the Apocynaceae and Rubiacae families 15 .…”

Section: Introductionmentioning

confidence: 99%

Antitumor properties of certain spirooxindoles towards hepatocellular carcinoma endowed with antioxidant activity

Al-Rashood

Hamed

Hassan

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

In the current medical era, spirooxindole motif stands out as a privileged heterospirocyclic scaffold that represents the core for a wide range of bioactive naturally isolated products (such as Strychnofoline and spirotryprostatins A and B) and synthetic compounds. Interestingly, no much attention has been paid to develop spirooxindole derivatives with dual antioxidant and anticancer activities. In this context, a series of spirooxindoles 6a-p was examined for their anticancer effect towards HepG2 hepatocellular carcinoma and PC-3 prostate cancer cell lines. Spirooxindole 6a was found to be an efficient anti-proliferative agent towards both HepG2 and PC-3 cells (IC50 ¼ 6.9 and 11.8 mM, respectively). Afterwards, spirooxindole 6a was assessed for its apoptosis induction potential in HepG2 cells, where its pro-apoptotic impact was approved via the significant elevation in the Bax/Bcl-2 ratio and the expression levels of caspase-3, ARTICLE HISTORY

show abstract

Synthesis and biological evaluation of certain hydrazonoindolin-2-one derivatives as new potent anti-proliferative agents

Cited by 50 publications

References 31 publications

Novel Thiazolidinone/Thiazolo[3,2-a]Benzimidazolone-Isatin Conjugates as Apoptotic Anti-proliferative Agents Towards Breast Cancer: One-Pot Synthesis and In Vitro Biological Evaluation

Novel Thiazolidinone/Thiazolo[3,2-a]Benzimidazolone-Isatin Conjugates as Apoptotic Anti-proliferative Agents Towards Breast Cancer: One-Pot Synthesis and In Vitro Biological Evaluation

Recent advances in isatin hybrids as potential anticancer agents

Antitumor properties of certain spirooxindoles towards hepatocellular carcinoma endowed with antioxidant activity

Contact Info

Product

Resources

About