Synthesis of Novel Class of &lt;i&gt;N&lt;/i&gt;-Alkyl-isatin-3-iminobenzoic Acid Derivatives and Their Biological Activity in Zebrafish Embryos and Human Cancer Cell Lines

Farooq, Muhammad; Marhoon, Zainab Mohammed Al; Taha, Nael Abu; Baabbad, Almohannad; Al-Wadaan, Mohammed A.; El‐Faham, Ayman

doi:10.1248/bpb.b17-00674

Cited by 15 publications

(13 citation statements)

References 32 publications

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“…456(±1.004) -0.383(±0.077) nArNO 2 +2.234(±0.432) nR09+ 5.417(±1.643) n COOH R 0.657 S.E = 0.32 F = 24.74 Q 2 = 0.62 RMScv = 0.15This equation could explain about 65.7% of the variance and predict 62% of the variance in pIC50 data. It has a root mean square error of 0.18.…”

mentioning

confidence: 82%

“…The biological data used in this study was the anti-cancer activity against MCF7, (in terms of -log IC 50 ), of a set of 109 isatin derivatives [43][44][45][46][47][48][49][50][51]. The data set was classified into calibration and prediction set by kenardston algorithm of the 20 prediction molecules from the spaces of the calculated descriptors.…”

Section: Data Setmentioning

confidence: 99%

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QSAR and Docking Study of Isatin Analogues as Cytotoxic Agents

Sabet

Khabnadideh

Fathi

et al. 2019

JPRI

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Computational chemistry is a unique method in the drug discovery process?? Explain Why?. In this study 109 molecules containing the isatin backbone were subjected to quantitative structure-activity relationship analysis to find the structure requirements for ligand binding. The structures were sketched and optimized in Hyperchem. The structural invariants used in this study were those obtained from whole molecular structures: by both hyperchem and dragon software (16 types of descriptors). Four chemometrics methods including MLR, FA-MLR, PCR and GA-PLS were employed to make connections between structural parameters and anticancer effects. MLR models revealed the effects of constitutional, functional, geometrical, WHIM and GETAWAY descriptors having higher impact on anticancer activity of the compounds. GA-PLS showed functional, constitutional and chemical descriptor indices to be the most significant parameters on anticancer activity. Moreover, the result of FA-MLR analysis revealed the effects of functional descriptors on the anticancer activity. A comparison between the different statistical methods employed and the results indicated that GA-PLS represented superior results and could explain and predict 81% and JPRI, 27(5): 1-22, 2019; Article no.JPRI.48076 2 78% variances in the PIC 50 data, respectively. Docking studies of these compounds were also investigated and promising results were obtained showing that some compounds were introduced as a good candidate for cancer agents. Original Research Article

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confidence: 82%

Section: Data Setmentioning

confidence: 99%

QSAR and Docking Study of Isatin Analogues as Cytotoxic Agents

Sabet

Khabnadideh

Fathi

et al. 2019

JPRI

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“…In addition to PABA "non-imine" cytotoxic derivatives [1,5,12,44], Farooq et al [18] discovered N-alkylisatin-3-iminobenzoic acids, i.e., Schiff bases of substituted isatin and PABA, as potential cytotoxic/antileukemic agents with IC 50 for human normal as well as cancer cell lines comparable to our the most active molecules. Thus, the formation of Schiff bases could convert non-toxic PABA to moderate cytotoxic agents, depending on the carbonyl compound used.…”

Section: Cytotoxicitymentioning

confidence: 96%

“…PABA-ambazone salt exhibited improved antibacterial effect when compared to parent drugs [17]. Schiff bases with isatin ( Figure 2, XII) exhibited activity against various cancer cell lines [18]. Thus, the chemical modification of PABA provides a viable concept for modulation of its properties to obtain both antimicrobial and cytotoxic compounds.…”

Section: Introductionmentioning

confidence: 99%

4-Aminobenzoic Acid Derivatives: Converting Folate Precursor to Antimicrobial and Cytotoxic Agents

et al. 2019

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4-aminobenzoic acid (PABA), an essential nutrient for many human pathogens, but dispensable for humans, and its derivatives have exhibited various biological activities. In this study, we combined two pharmacophores using a molecular hybridization approach: this vitamin-like molecule and various aromatic aldehydes, including salicylaldehydes and 5-nitrofurfural, via imine bond in one-step reaction. Resulting Schiff bases were screened as potential antimicrobial and cytotoxic agents. The simple chemical modification of non-toxic PABA resulted in constitution of antibacterial activity including inhibition of methicillin-resistant Staphylococcus aureus (minimum inhibitory concentrations, MIC, from 15.62 µM), moderate antimycobacterial activity (MIC ≥ 62.5 µM) and potent broad-spectrum antifungal properties (MIC of ≥ 7.81 µM). Some of the Schiff bases also exhibited notable cytotoxicity for cancer HepG2 cell line (IC 50 ≥ 15.0 µM). Regarding aldehyde used for the derivatization of PABA, it is possible to tune up the particular activities and obtain derivatives with promising bioactivities.

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“…The isatin–imine hybrids 6 (Figure 4; IC 50 : 7.8–91 μM; 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide [MTT] assay) showed considerable activity against MCF‐7, HepG2, and Jurkat cancer cell lines and the SAR revealed that introduction of benzyl into N‐1 position of isatin moiety was beneficial to the activity. [ 39,40 ] Further study indicated that incorporation of morpholinosulfonyl into the C‐5 position of isatin skeleton was also tolerated and hybrids 7 (IC 50 : 10.39–55.90 μM, SRB assay) displayed potential activity against HepG2, HCT‐116, CACO, and MCF‐7 cancer cell lines, but the activity was not superior to that of doxorubicin (IC 50 : 4.56–8.29 μM). [ 41,42 ] The activity of hybrids 6a,b (IC 50 : 7.8–66 μM) was comparable to or better than that of the references 5‐fluorouracil (IC 50 : 38 to >100 μM) and semaxanib (IC 50 : 41.39 to >100 μM) against the three cancer cell lines and these two hybrids (IC 50 : >100 and 91.53 μM, respectively) were also less toxic than 5‐fluorouracil (IC 50 : 37.87 μM) and semaxanib (IC 50 : 21.86 μM) against normal HFF‐1 cells.…”

Section: Isatin–coumarin Hybridsmentioning

confidence: 99%

Recent advances in isatin hybrids as potential anticancer agents

Ding

Zhou

Zeng

2020

Archiv der Pharmazie

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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 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.

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Synthesis of Novel Class of <i>N</i>-Alkyl-isatin-3-iminobenzoic Acid Derivatives and Their Biological Activity in Zebrafish Embryos and Human Cancer Cell Lines

Cited by 15 publications

References 32 publications

QSAR and Docking Study of Isatin Analogues as Cytotoxic Agents

QSAR and Docking Study of Isatin Analogues as Cytotoxic Agents

4-Aminobenzoic Acid Derivatives: Converting Folate Precursor to Antimicrobial and Cytotoxic Agents

Recent advances in isatin hybrids as potential anticancer agents

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