Synthesis and Biological Evaluation of 4‐Arylphthalazones Bearing Benzenesulfonamide as Anti‐Inflammatory and Anti‐Cancer Agents

Abstract

Nine 4-arylphthalazones bearing benzenesulfonamide (2a-i) were synthesized by the condensation of the appropriate 2-aroylbenzoic acid (1a-i) and 4-hydrazinobenzenesulfonamide in ethanol. The structures of these compounds were elucidated by elemental analysis, IR, ¹H NMR, ¹³C NMR, and MS spectroscopy. Two compounds, 2b and 2i, showed significant anti-inflammatory activity comparable to that of the standard drug celecoxib in the carrageenan-induced rat paw edema model. These compounds (2b and 2i) had selective inhibitory activity towards the COX-2 enzyme. Compound 2b had a better selectivity ratio (COX-1/COX-2) compared to that of celecoxib and can be used as a novel template for the design of selective COX-2 inhibitors. Compounds 2d and 2i were screened for their antiproliferative activity toward 60 human cancer cell lines by the National Cancer Institute (USA). The compounds 2d and 2i displayed mild activity toward the renal cancer cell line UO-31.

ADMET Prediction of synthesized Heterocyclic derivatives to treat renal cancer

“…The growth inhibition percentage of compounds 82-89 was found to be above 35% against renal cancel cell lines RXF393 and ACHN [31]. Compounds 92 and 93 showed IC50 values below 10 µm against renal cancer cell line UO-31 [33].…”

“…An extensive review study was carried out on heterocyclic derivatives designed, synthesized, characterized, and evaluated against renal carcinoma cell lines. The study focused on selecting potent compounds from the synthesized heterocyclic moieties such as pyrimidine [16][17][18][19][20][21][22], phthalazine [23], benzothiazole [24], Benzpyrazoline [25,26], indoline [27][28][29][30][31], benzimidazole [32], phthalazone [33], indole [34,35], quinoline [36,37], quinazoline [38] based on their IC50 value and cell inhibition (%) against renal cancer cell line such as 786-O, A-498, TK-10, UO-31, ACHN, SKNEP-1, HEK-293, CAK-1, RCC, 760-O, RXF393, SN12C and CAKi-1. Around 648 synthesized compounds were studied, and 121 potent compounds were selected.…”

“…Around 60% of the medications used for cancer treatment are based on heterocyclic moieties [13]. Heterocyclic compounds like pyrimidine [16][17][18][19][20][21][22], phthalazine [23], benzothiazole [24], Benzpyrazoline [25,26], indoline [27][28][29][30][31], benzimidazole [32], phthalazone [33], indole [34,35], quinoline [36,37], quinazoline [38] find application in the treatment of renal cancer. Many synthetic nitrogen heterocycles are extremely relevant to pharmacology and medicine.…”