Palestinian Medical and Pharmaceutical Journal (Pal. Med. Pharm. J.)

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Keywords

• EGFR inhibitors
• A549 Cell Line
• Pyrazole Derivatives
• NSCLC
• Cytotoxicity
• Ultrasound-Assisted Synthesis

Abstract

Non-small-cell lung cancer (NSCLC) accounts for the majority of lung-cancer deaths, largely driven by dysregulated epidermal growth factor receptor (EGFR) signaling that promotes uncontrolled proliferation and survival. While EGFR tyrosine-kinase inhibitors (TKIs) have provided significant therapeutic benefit, challenges related to resistance and tolerability highlight the need for novel compounds with improved binding interactions and favorable drug-like characteristics. A novel series of pyrazole-based carbamothioyl compounds was synthesized and tested for their anticancer activity against non-small-cell lung carcinoma (NSCLC). The compounds were prepared via an ultrasound-assisted synthetic route involving acyl chloride formation, thiocyanation, and subsequent coupling with substituted aminopyrazoles. The structural features of the synthesized compounds were verified using FTIR, ¹H NMR, and ¹³C NMR techniques. Their cytotoxic behavior was evaluated in A549 lung cancer cells through the MTT method following incubation intervals of 24, 48, and 72 hours. All compounds exhibited dose- and time-dependent antiproliferative effects, with compounds H2 and H5 showing the highest potency at 72 hours, yielding IC₅₀ values of 11.88 and 12.49 µg/mL, respectively—both more active than the standard drug erlotinib (IC₅₀ = 13.53 µg/mL). Morphological evaluation revealed characteristic features of apoptosis and necrosis, including cell shrinkage and chromatin condensation. These findings indicate that all synthesized derivatives possess promising cytotoxic activity and promising lead compounds for further development in targeted lung cancer therapy.

معلومات المقال

قيد النشر

الكلمات الإفتتاحية

• EGFR inhibitors
• A549 Cell Line
• Pyrazole Derivatives
• NSCLC
• Cytotoxicity
• Ultrasound-Assisted Synthesis

الملخص

Non-small-cell lung cancer (NSCLC) accounts for the majority of lung-cancer deaths, largely driven by dysregulated epidermal growth factor receptor (EGFR) signaling that promotes uncontrolled proliferation and survival. While EGFR tyrosine-kinase inhibitors (TKIs) have provided significant therapeutic benefit, challenges related to resistance and tolerability highlight the need for novel compounds with improved binding interactions and favorable drug-like characteristics. A novel series of pyrazole-based carbamothioyl compounds was synthesized and tested for their anticancer activity against non-small-cell lung carcinoma (NSCLC). The compounds were prepared via an ultrasound-assisted synthetic route involving acyl chloride formation, thiocyanation, and subsequent coupling with substituted aminopyrazoles. The structural features of the synthesized compounds were verified using FTIR, ¹H NMR, and ¹³C NMR techniques. Their cytotoxic behavior was evaluated in A549 lung cancer cells through the MTT method following incubation intervals of 24, 48, and 72 hours. All compounds exhibited dose- and time-dependent antiproliferative effects, with compounds H2 and H5 showing the highest potency at 72 hours, yielding IC₅₀ values of 11.88 and 12.49 µg/mL, respectively—both more active than the standard drug erlotinib (IC₅₀ = 13.53 µg/mL). Morphological evaluation revealed characteristic features of apoptosis and necrosis, including cell shrinkage and chromatin condensation. These findings indicate that all synthesized derivatives possess promising cytotoxic activity and promising lead compounds for further development in targeted lung cancer therapy.