Visible-light promoted catalyst-free (VLCF) multi-component synthesis of spiro indolo-quinazolinone-pyrrolo[3,4-a]pyrrolizine hybrids: evaluation of in vitro anticancer activity, molecular docking, MD simulation and DFT studies

被引：6

作者：

Iqbal, Safia ^{[1
]}

Farhanaz ^{[1
]}

Roohi ^{[2
]}

Zaheer, Mohd. Rehan ^{[3
]}

Shankar, Krapa ^{[4
]}

Hussain, Mohd. Kamil ^{[5
]}

Zia, Qamar F. ^{[6
]}

Rehman, Md. Tabish ^{[7
]}

AlAjmi, Mohamed ^{[7
]}

Gupta, Anamika ^{[1
,8
]}

机构：

[1] Aligarh Muslim Univ, Dept Chem, Aligarh, India

[2] Integral Univ, Dept Bioengn, Prot Res Lab, Lucknow, India

[3] RMPSP Girls Post Grad Coll, Dept Chem, Basti, India

[4] Sun Pharmaceut Ind Ltd, Sect 18, Gurgaon, India

[5] Govt Raza PG Coll, Dept Chem, Rampur, India

[6] Majmaah Univ, Coll Appl Med Sci, Dept Med Lab Sci, Al Majmaah, Saudi Arabia

[7] King Saud Univ, Coll Pharm, Dept Pharmacognosy, Riyadh, Saudi Arabia

[8] Aligarh Muslim Univ, Dept Chem, Aligarh 202002, Uttar Pradesh, India

来源：

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS | 2024年 / 42卷 / 06期

关键词：

visible-light catalyst-free (VLCF); EDA complex; azomethine ylide; spiro-fused; anticancer; DFT study; molecular docking; MD simulation; environment-friendly; ANTI-BREAST CANCER; ASYMMETRIC 1,3-DIPOLAR CYCLOADDITIONS; TYROSINE KINASE INHIBITOR; TRANSITION METAL-FREE; AZOMETHINE YLIDES; ENANTIOSELECTIVE CONSTRUCTION; ONE-POT; INTERMOLECULAR INTERACTIONS; HIRSHFELD SURFACES; CRYSTAL-STRUCTURE;

D O I：

10.1080/07391102.2023.2214229

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A new and highly efficient visible-light-promoted catalyst free (VLCF) strategy for neat and clean synthesis of spiro indolo-quinazolinone-pyrrolo[3,4-a]pyrrolizine hybrids (6a-d) has been introduced. We have performed visible-light triggered 1,3-Dipolar cycloaddition reaction of maleimide (5a-d) with azomethine ylide generated in situ derived from tryptanthrin (3) and L-proline (4) to obtain desired products (6a-d) in good to excellent yield. Authentication and characterization of product was done using various spectroscopic techniques such as IR, H-1 NMR, C-13 NMR, Mass spectrometry and single crystal XRD analysis. To explain the reaction spontaneity, product stability, reactivity as well as possible mode of the interaction a quantum chemical investigation was performed and depicted through DFT studies. The synthesized compound 6a was also evaluated for anti-proliferative activity against a panel of five cancer cell lines (MCF-7, MDA-MB-231, HeLa, PC-3 and Ishikawa) and normal human embryonic kidney (HEK-293) cell line by using MTT assay. Compound 6a showed very good in vitro anti-proliferative activity (IC50 = 6.58-17.98 mu M) against four cancer cell lines and no cytotoxicity against normal HEK-293. In order to evaluate the anticancer potential of compounds 6a-d, molecular docking was performed against wild type and mutant EGFR. The results suggest that all the compounds occupied the active site of both enzymes, with a strong binding energy (-10.2 to -11.5 kcal/mol). These results have been confirmed by molecular dynamics simulation by evaluating root mean square deviation (RMSD) and root mean square fluctuation (RMSF), along with principal component analysis (PCA).Communicated by Ramaswamy H. Sarma

引用

页码：3145 / 3165

页数：21