In-vitro Evaluation of Isatin Derivatives as Potent Anti-Breast Cancer Agents against MCF-7, MDA MB 231, MDA-MB 435 and MDA-MB 468 Breast Cancers Cell Lines: A Review

Abstract

Introduction: Breast cancer (BC) is one of the most frequent malignancy and most common reasons of impermanence in women. The backbone of therapy for BC is principally chemotherapy, but due to its non-specific nature between normal cells and cancer cells and severe side effects are the main barriers in its therapy. So, there is an intense requirement for the enlargement of more efficacious, more specific and safer anti-BC agents. Objective: Isatin (IST) is an endogenous molecule which is a principal class of heterocyclic compounds and exhibits a wide range of therapeutic activities which can be used as a starting material for the synthesis of several drug molecules. Many literatures were reported previously on different pharmacological activities of IST derivatives and particularly on anticancer activity but this review mainly focus on anti-BC activities of IST derivatives through MCF-7, MDA MB 231, MDA-MB 435 and MDA-MB 468 cell lines. Here in we mentioned, a total 33 IST derivatives (compound 24- 56) which shown good anti-BC activity. IST derived compounds are also available in market and are used for various cancer types like sunitinib for renal cell carcinoma (RCC) and Nintedanib used for the cryptogenic fibrosing alveolitis treatment but when evaluated for BC did not get much success. Conclusion: This review mainly highlights anti-BC activities of various IST analogues using MCF-7, MDA MB 231, MDA-MB 435 and MDA-MB 468 cell lines, display the potent compound of the series and structure-activity relationships of compounds with molecular docking also. So, this study mainly shows the importance of IST as major sources for drug design and development of newer anti-BC drugs.

Step-Economic Total Synthesis of Melosatin A from Eugenol

“…23a It can be conjectured that the reaction could proceed through an initial nucleophilic attack of the aniline (25) to one of the ester moieties of an alkyl-2ketomalonate (mesoxalic ester 26) in AcOH to provide the amide i. In turn, this intermediate could cyclize under the promotion of the electron pair of the nitrogen atom, to afford species ii, resulting from isomerization or a [1,3]-hydrogen shift that regenerates the aromatic ring. Subsequent treatment with aqueous 1 M KOH, would cause hydrolysis of the ester and triggers the decarboxylation of the 1,3-dicarbonyl intermediate iii to deliver the 3-hydroxyindolinone (iv).…”

“…11 We also realized that certain 4-substituted isatins like 9 induce dopaminergic or D2-agonist activity useful for treating hypertension 12a and others such as 10 proved to be relevant inhibitors of enzyme CDK2. 12b As a result, we became interested in melosatin A (1), which is reminiscent of 7−10 and shares structural similarity with the substitution pattern of the carbocyclic ring of melovinone (5). Remarkably, being cooccurring metabolites, Kapadia et al suggested a plausible common biogenetic origin for 1 and 5.…”

Design, synthesis and anti-breast cancer properties of butyric ester tethered dihydroartemisinin-isatin hybrids

“…Isatin, widely distributed in natural kingdom, is a well-known pharmacologically active scaffold [ 17 , 18 ]. Isatin hybrids possessed significant therapeutic effect on breast cancers including drug-resistant forms, good selectivity and low toxic side effects [ 19 , 20 ]. Recent studies demonstrated that DHA-isatin hybrids exhibited promising antiproliferative activity against both drug-sensitive and drug-resistant cancer cell lines [ 21 – 24 ].…”

Design, Synthesis, and Biological Evaluation of Novel Amyl Ester Tethered Dihydroartemisinin‐Isatin Hybrids as Potent Anti‐Breast Cancer Agents

“…The recent studies revealed that DHA‐isatin hybrids possessed potential antiproliferative activity against both drug‐sensitive and drug‐resistant breast cancer cell lines, revealing that rational design of DHA‐isatin hybrids may provide novel anti‐breast cancer candidates [21,22] . The structure–activity relationship illustrated that the linker between DHA and isatin was critical for the antiproliferative activity of DHA‐isatin hybrids, and hybrids with alkyl linkers were generally more active than the 1,2,3‐triazole tethered analogs [19,20] . Ester is easy to hydrolyze, so the ester tethered DHA‐isatin hybrids may could act as prodrugs.…”

“…However, the therapeutic efficacy of DHA is compromised owing to its inherent disadvantages such as poor stability and low aqueous solubility [17,18] . Isatin, an endogenous molecule, could act on various biological targets, and its derivatives possessed profound in vitro and in vivo efficacies against various cancers including drug‐sensitive and multidrug‐resistant breast cancers [19,20] . Accordingly, isatin is a fruitful matrix for the development of novel anti‐breast cancer agents.…”