Evaluation of antitumor potential of synthesized novel 2-substituted 4-anilinoquinazolines as quinazoline-pyrrole hybrids in MCF-7 human breast cancer cell line and A-549 human lung adenocarcinoma cell lines

Abstract

Background: A series of novel 2 substituted 4-anilinoquinazolines-pyrrole hybrids were synthesized, and cytotoxic activity were evaluated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Methods: The cell line used for the activity was MCF-7 breast cancer cell line and A459 human lung adenocarcinoma cell line. The newly quinazoline-pyrrole hybrid compounds have been synthesized from the 4chloro-7-(3-chloropropoxy)-6-methoxy-2-phenylquinazoline derivatives. The chemical structure of the synthesized compounds has been confirmed by FTIR, 1 HNMR, 13 C NMR, and mass spectral data. The cytotoxic study was conducted using morphological study and MTT assay against adenocarcinoma and human breast cancer cell lines. Results: The results of cytotoxic evaluation revealed that few compounds show moderate to promising activity when compared with standard doxorubicin (IC 50 value 41.05 μM at 72 h). The synthesized compounds 7d and 7f were found effective in breast cancer cell line with IC 50 values 40.64 μM and 44.98 μM at 72 h, respectively. The synthesized compounds 7d, 7f, 7g, and 7h were found effective in adenocarcinoma cell line with IC 50 values of 41.05 μM, 45.54 μM, 46.93 μM, and 48.62 μM, respectively. Conclusion: Based on the experimental evidences, we proposed structure activity relationship to provide significant information for the design and development of further potent anticancer agents.

MSCs as Tumor-Specific Vectors for the Delivery of Anticancer Agents—A Potential Therapeutic Strategy in Cancer Diseases: Perspectives for Quinazoline Derivatives

“…In recent years, The Food and Drug Administration (FDA) has approved several quinazoline derivatives as a new class of cancer chemotherapeutic agents with significant therapeutic efficacy against solid tumors. Anticancer drugs such as gefitinib ( 8 ), erlotinib, lapatinib ( 9 ), afatinib ( 10 ), and vandetanib were approved for clinical use ( Figure 3 ) [ 114 ]. However, the potential of quinazolines is still being researched, and new therapeutic approaches for their use are also being sought.…”

“…The expression of ABC transporters is often associated with the occurrence of MDR in chemotherapy of multiple cancers [ 135 , 136 ]. Quinazolines have also been shown to exhibit satisfactory cytotoxic activity and can significantly inhibit the proliferation of different human cancer cell lines such as MCF-7, BT-474 and MDA-MB231 human breast cancer cell lines, the A-549 human lung adenocarcinoma cell line, the HeLa cervical cancer cell line, the HT-29 human colorectal adenocarcinoma cell line, the A375 melanoma cancer cell line and the D283 medulloblastoma cell line [ 114 , 137 , 138 , 139 , 140 ].…”

Quinazoline Derivatives as Potential Therapeutic Agents in Urinary Bladder Cancer Therapy

“…They have demonstrated significant therapeutic efficacy, especially against solid tumors. Many are approved for antitumor clinical use, e.g.,: erlotinib (N-(3-Ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine) (Figure 1 (Bathula et al, 2020). The antitumor effects of quinazolines can manifest through numerous pathways.…”

“…They have demonstrated significant therapeutic efficacy, especially against solid tumors. Many are approved for antitumor clinical use, e.g.,: erlotinib ( N -(3-Ethynylphenyl)-6,7-bis(2- methoxyethoxy)quinazolin-4-amine) ( Figure 1 : 5), gefitinib (N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine) ( Figure 1 : 6), afatinib ((E)-N-[4-(3-chloro-4-fluoroanilino)-7-[(3S)-oxolan-3-yl]oxyquinazolin-6-yl]-4-(dimethylamino)but-2-enamide) ( Figure 1 : 7), lapatinib (N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine) ( Figure 1 : 8), vandetanib (N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine) ( Figure 1 : 9) ( Bathula et al, 2020 ). The antitumor effects of quinazolines can manifest through numerous pathways.…”

“…Recently attempts have been made to synthetize a compound using a pyrrole ring. The obtained 2-substituted 4-anilinoquinazoline-pyrrrole conjugates ( Figure 3 : 18) showed moderate antiproliferative potency against the MCF-7 and A-549 cells ( Bathula et al, 2020 ).…”