Adenosine is known as an endogenous purine nucleoside and it modulates a wide variety of physiological responses by interacting with adenosine receptors. Among the four adenosine receptor subtypes, the A3 receptor is of major interest in this study as it is overexpressed in some cancer cell lines. Herein, we have highlighted the strategy of designing the hA3 receptor targeted novel benzothiazolylquinoline scaffolds. The radioligand binding data of the reported compounds are rationalized with the molecular docking results. Compound 6a showed best potency and selectivity at hA3 among other adenosine receptors. © 2018 The Authors.

Priyankar Paira

Department of Chemistry

School of Advanced Sciences

Vellore Campus

Sarkar B

Maiti S

Jadhav G.R

Fulltext

Vellore Institute of Technology (VIT) is a private university located in&nbsp;Tamil Nadu, India. Founded in 1984, as Vellore Engineering College, the institution offers 20 undergraduate, 34 postgraduate, four integrated and four research programs. It has campuses in Vellore, Amravati, Bhopal and Chennai.

VIT is one of the top ranked private universities in India according to NIRF, THE and QS Rankings.&nbsp;Govt. of India has recognized&nbsp;VIT, Vellore as an&nbsp;Institution of Eminence. This has allowed VIT to take independent quality initiatives and move up in world ranking.

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VIT University

Royal Society Open Science

Xenobiotics good pharmacodynamic effect should be evaluated with acceptable drug like properties during the drug discovery process. Benzothiazolyl-quinoline derivatives are with reported biological and anticancer activity. In the present study, compounds were screened for potency determination in Caco-2 (Human Epithelial Colorectal Adenocarcinoma) cell line and the most potent compound was evaluated through some of the drug development assays. Experimental protocols were set for stability and solubility (in buffer pH 7.4), metabolic stability, metabolite profiling, Caco-2 permeability, P-gp (P-glycoprotein) inhibition in MDCK (Madin-Darbey Canine Kidney)-MDR1 overexpressed cells and CYP induction study by using LC-MS/MS(Liquid Chromatography Tandem Mass spectrometry) method. The compound was stable and soluble in buffer pH 7.4, less permeable across Caco-2 cell monolayer, unstable in microsomes, inhibitor of efflux P-gp transporter and an inducer CYP (Cytochrome P450) 1 A2. The most potent compound (i. e. 6 k) was with high solubility, low permeability and high CL int (intrinsic clearance) in liver microsomes. Therefore it was preliminary classified as class III compound as per biopharmaceutics classification system (BCS) and Class I compound as per biopharmaceutical drug disposition classification system (BDDCS). © 2019 Wiley-VCH Verlag GmbH &amp; Co. KGaA, Weinheim

ChemistrySelect

Cytotoxic 2‐(2′‐Hydroxyphenyl)benzothiazolylquinoline Analogues and their In Vitro Screening through Developmental Assays †

A series of luminescent bis(benzo[d]thiazolyl)quinoxalines have been synthesized and their fluorescence properties, anticancer potency, DNA and BSA interactions, cellular uptake, and metabolic stabilities are investigated.

RSC Advances

Luminescent bis(benzo[d]thiazolyl)quinoxaline: facile synthesis, nucleic acid and protein BSA interaction, live-cell imaging, biopharmaceutical research and cancer theranostic application

We have demonstrated a novel and green approach for the synthesis of 2-substituted benzothiazole analogues. A number of 2-aryl and heteroaryl benzothiazole scaffolds were synthesized using Amberlite IR-120 resin under microwave irradiation. The catalytic role and reusability of the resin was well established here. 2-Substituted benzothiazole analogues (3a-l) were also tested against several bacterial strains (Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella) and cancer cell lines (MCF-7 and HeLa). The stability of compound 2-phenyl benzothiazole (3a) and 2-pyridin-2-yl-benzothiazole (3k) in GSH (0.01 mM dissolved in DMSO) was measured by UV-Vis spectroscopy. Compound 3k also shows remarkable fluorescence in MeOH. © 2015 Elsevier Ltd.

Bioorganic & Medicinal Chemistry Letters

An efficient green synthesis of 2-arylbenzothiazole analogues as potent antibacterial and anticancer agents

In the present study, a molecular simplification approach was employed to design novel bicyclic pyrazolo[3,4-d]pyrimidine (PP) derivatives from tricyclic pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidines (PTP) as promising human A3 adenosine receptor (hA3AR) antagonists. All the target compounds were synthesized using novel and efficient synthetic schemes and the structure-activity relationship studies of these PPs were explored through the synthesis of a series of PTP analogues with various substituents. Substituents with different lipophilicity and steric hindrance (e.g., alkyl and aryl-alkyl) functions were introduced at N2 position of the pyrazole ring, while acyl groups with different electronic properties were introduced at C 6 position of the bicyclic nucleus to probe both electronic and positional effects. Most of the synthesized derivatives of the PP series presented good affinity at the hA3AR, as indicated by the low micromolar range of Ki values and among them, compound 63 with N 2 neopentyl substituents showed most potent hA3AR affinity with Ki value of 0.9 μM and high selectivity (hA 1AR/hA3AR = &gt;111 &amp; hA2AAR/hA 3AR = &gt;111) towards other adenosine receptor subtypes. Interestingly, small isopropyl groups at N2 position displayed high affinity at another receptor subtype (hA2AAR, e.g., compound 55, with Ki hA2AAR = 0.8 μM), while they were less favorable at the hA3AR. Molecular docking analysis was also performed to predict the possible binding mode of target compounds inside the hA3AR and hA2AAR. Overall, PP derivatives represent promising starting points for new AR antagonists. © 2014 Elsevier Ltd. All rights reserved.

Bioorganic & Medicinal Chemistry

Discovery of simplified N2-substituted pyrazolo[3,4-d]pyrimidine derivatives as novel adenosine receptor antagonists: Efficient synthetic approaches, biological evaluations and molecular docking studies

Amberlite IRA 402(OH) Mediated Green Synthesis of Novel Benzothiazole–quinoline Conjugates as Cancer Theranostics

1,2,4-Triazolo[1,5-a]quinoxaline derivatives and their simplified analogues as adenosine A3 receptor antagonists. Synthesis, structure–affinity relationships and molecular modeling studies

Journal	Data powered by TypesetRoyal Society Open Science
Publisher	Data powered by TypesetThe Royal Society
ISSN	2054-5703
Impact Factor	1.531
Open Access	Yes
Citation Style	Vancouver
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