Design, synthesis, and anticancer evaluation of acetamide and hydrazine analogues of pyrimidine

Abstract

A library of acetamide and hydrazine analogues were generated on the pyrimidine ring through a multistep reaction starting from 5‐nitro‐pyrimidine‐4,6‐diol and pyrimidine‐4,6‐diol, respectively. The synthesized analogues were screened for in vitro cytotoxic activity against various human cancer cell lines like HCT‐1 and HT‐15 (colon), MCF‐7(breast), PC‐3 (prostrate), SF268 (CNS) using MTT method. From the bioassay results, it was observed that even though many of the synthesized derivatives exhibited a good potency against various screened cancer cell lines, compound 14a from the acetamide series was found to show potent anticancer activity on all the tested cancer cell lines with IC50 value of 0.36μM on CNS cell line and 1.6μM on HT‐21 cell line, and compound 19xxi from hydrazine series of pyrimidine showed potent activity against three tested cancer cell lines with IC50 value of 0.76μM on HT‐29 cell line, 2.6μM on HCT‐15, and 3.2μM on MCF‐7 cell line.

Recent investigations into synthesis and pharmacological activities of phenoxy acetamide and its derivatives (chalcone, indole and quinoline) as possible therapeutic candidates

“…Therefore, special attention has also been given to acetamide medications because of their possible use as a therapeutic agent. Acetamide derivatives and their analogs representing a high potential of biological activities including anti-inflammatory [ 63 ], anti-oxidant [ 64 ], anti-cancer [ 65 ], anti-convulsant [ 66 ], anti-hypoxic and anti-microbial [ 67 ], antituberculosis agents [ 68 ] and anti-COVID-19 molecules [ 69 ]. In addition, several acetamide derivatives are used to improve some enzymes that inhibit HIV virus activity from replicating [ 70 ].…”

“…Many chalcones also can be obtained via coupling reactions by using different reactants (63)(64)(65)(66)(67)(68)(69). Several reactions involved C-C and C-heteroatom covalent bond via oxidative addition transmetalation-reductive elimination, as illustrated in Scheme 12 [93].…”

Utility of 2-Chloro-N-arylacetamide and 1,1′-(Piperazine-1,4-diyl)bis(2-chloroethanone) as Versatile Precursors for Novel Mono- and Bis[thienopyridines]

“… 17 In terms of medicine, roughly one-quarter of all marketed drugs (and two-thirds of all drug candidates) contain at least one amide bond. 18 Furthermore, molecules with an acetamide linkage or its derivatives as core structures have received significant attention due to their potential therapeutic applications as anti-inflammatory, 19 anticancer, 20 analgesic, 21 antimicrobial, 21 − 23 anticonvulsant, 24 antituberculosis agents, 25 and anti-COVID-19 agents. 26 Some acetamide derivatives, such as paracetamol V 27 ( Figure 1 ), have been shown to have analgesic or sedative properties.…”

Synthesis of novel thiazole, imidazole, benzimidazole, and benzothiazole derivatives incorporating 2‐phenoxy‐N‐arylacetamide unit as novel hybrid molecules

“…Moreover, it was reported that molecules with an acetamide linkage or its derivatives have gotten much attention due to their potential therapeutic applications, including anticancer [3], analgesic [4,5], antimicrobial [6], anticonvulsant [7], antituberculosis agents [8], and anti-COVID-19 agents [9]. Furthermore, in recent decades, thiazole derivatives have received a lot of attention.…”