Synthesis of arylpyrazole linked benzimidazole conjugates as potential microtubule disruptors

Synthesis, Crystal Study, and Anti-Proliferative Activity of Some 2-Benzimidazolylthioacetophenones towards Triple-Negative Breast Cancer MDA-MB-468 Cells as Apoptosis-Inducing Agents

“…Structures of some reported benzimidazoles I – VIII , by other research groups, with anti-proliferative activity against triple-negative breast cancer MDA-MB-468 cells [22,23,24,25,26,27]. …”

“…Attaching a heterocyclic moiety, 5- tert -butyl-1 H -pyrazol-3-yl, in position 1 and an aryl moiety, 4-chlorophenyl, in position 2 of benzimidazole core resulted in compound I (NSC: 751047) with good anti-proliferative activity against MDA-MB-468 (IC 50 = 2.4 µM) [22] (Figure 1), while substitution of position 2 of 5-flouro and 5-methoxybenzimidazole with 1,2,4-oxadiazole moiety through a phenyl ring afforded compounds II and III , respectively, (NSC: 761109 and 761814) with IC 50 values of 3.01 and 6.54 µM, respectively, against MDA-MB-468 [23] (Figure 1). Moreover, introduction of different aryl groups through a pyrazole linker at position 2 of the benzimidazole core, as in compounds IV and V (NSC: 768400 and 768399), achieved significant efficacy against MDA-MB-468 (IC 50 values of 0.93 and 3.5 µM, respectively) [24] (Figure 1). Interestingly, linking different aryl moeities, through variable heterocyclic groups, via a three-atom linker, namely a propan-1-one group to position 2 of the benzimidazole core led to compounds VI – VIII (NSC: 761980, NSC: 759205 and NSC: 7604520) with low or sub-micromolar anti-proliferative activity against MDA-MB-468 (IC 50 = 1.93, 0.79 and 0.69 µM, respectively) [25,26,27] (Figure 1).…”

Study on Synthesis, Characterization and Antiproliferative Activity of Novel Diisopropylphenyl Esters of Selected Fatty Acids

“…The synthesized test compounds were evaluated for their in vitro antiproliferative activity in these five different human cancer cell lines followed by literature method 42 . A protocol of 48 hrs continuous drug exposure was used, and a SRB cell proliferation assay was used to estimate cell viability or growth.…”

Design and synthesis of pyrazole/isoxazole linked arylcinnamides as tubulin polymerization inhibitors and potential antiproliferative agents

“…These were oxidized to the pyrazole carbaldehydes (11a-d) by using IBX in DMSO. 24 These pyrazole carbaldehydes upon reaction with (carbethoxymethylene)triphenylphosphine, Ph 3 PCHCO 2 C 2 H 5 (C2-Wittig salt) in toluene afforded α,β-unsaturated esters 12a-d that subsequently underwent a base hydrolysis to give α,β-unsaturated carboxylic acids 13a-d. 26,27 Finally, these carboxylic acids conveniently coupled with substituted arylamines 14a-d in the presence of EDC/ Hobt produce the desired pyrazole linked phenylcinnamides (PP). 19 By employing the same methodology isoxazole linked (1), combretastatin-A4 (2), nocodazole (3), phenylcinnamides (4), thiadiazole ring based cinnamide (5), acrylylpiperazine (6) phenylcinnamide conjugates 21a-n were synthesized starting from isoxazole esters (16a-d) as shown in Scheme 2.…”

“…[21][22][23] Previously we have reported that a series of pyrazole based conjugates have shown profound cytotoxic effects by arresting the cells in the G2/M phase. [24][25][26] In view of the attractive biological activities exhibited by them, considerable interest in the development of newer cytotoxic agents has been aroused. The present work illustrates the design and synthesis of some pyrazole/isoxazole linked arylcinnamide conjugates and evaluates their ability to inhibit the growth of a panel of four human cancer cell lines.…”