Synthesis of Potent Anticancer Substituted 5-Benzimidazol-2-amino Thiazoles Controlled by Bifunctional Hydrogen Bonding under Microwave Irradiations

Abstract

Benzimidazol-amino thiazoles are synthesized under microwave irradiations using benzimidazole phenyl thiourea and 2bromoacetophenone. Bifunctional hydrogen bonding plays an important role in chemical conversion. The reaction was carried out by C−C bond formation, followed by C−N bond cleavage and simultaneous migration of the benzimidazole ring. This reaction is novel and efficient for the synthesis of benzimidazol-amino thiazoles in which microwaves were used as driving forces. Synthesis of the product was controlled by double hydrogen bonding which is practically confirmed by the synthesis of routine imino-thiazole as an alternative product in the simple acidic condition. The simple acidic condition is neither responsible nor sufficient for optimum conversion of the benzimidazole migrated product. The synthesized products benzimidazole amino thiazoles D4 (IC 50 = 4.207 μM) and D8 (IC 50 = 2.398 μM) show interesting anticancer activities for human lung cancer with reference to doxorubicin (IC 50 = 1.750 μM).

One Pot Catalyst‐free Synthesis of Substituted Di‐amino N‐tosyl Benzoyl Thiazoles byRegioselective C−N Bond Cleavage and Its Anticancer Activity

“…In continuation of our ongoing research forthe synthesis of the benzimidazole heterocyclic compounds with their mechanistic studies, [11] we focused on the synthesis of benzimidazol-2-imino diphenyl thiazolidin-4-ol (B1) hemiaminals (carbinolamine).This hemiaminal (B1) prepared by solid-phase reactive chromatography and utilized it as starting material in our recently published work [12] for the synthesis of 5-benzimidazol-2-iminodiphenyl thiazoles under microwave irradiations by the migration of the benzimidazole ring. The reaction was well controlled by bifunctional hydrogen bonding (Scheme 2).…”

“…The reaction was well controlled by bifunctional hydrogen bonding (Scheme 2). [12] The impressive result of this reaction envisaged that we can easily develop CÀ C bond formation reaction at guanidino carbon of benzimidazole ring. With the aim to explore the novelty in the chemistry of CÀ C bond formation at guanidine carbon of benzimidazole ring, we begin with N-tosylation on benzimidazole ring (Scheme 2).…”

Benzimidazole hybrids as anticancer drugs: An updated review on anticancer properties, structure–activity relationship, and mechanisms of action (2019–2021)

“…The benzimidazole-thiazole hybrids exhibited considerable antiproliferative activity, [49][50][51][52] and among them, hybrid 19 (Figure 4; IC 50 : 2.4-12.0 µM, MTT assay) was active against HT-29, DU145, A549, and MDA-MB-231 cancer cell lines and the activity was comparable to that of doxorubicin (IC 50 : 1.8 µM) against A549 cells. [52] The SAR indicated that the introduction of hydrazine into thiazole moiety was permitted and hybrid 20 (IC 50 : 6.3 µM, MTT assay) was not inferior to erlotinib (IC 50 : 4.2 µM) against MCF-7 cells. [53] Mechanistically, hybrid 20 induced apoptotic effect and cell cycle arrest at the G2/M phase, upregulated caspase-3, p53, Bax/Bcl- (IC 50 : 2.1 µM) against HeLa cells.…”

Design, synthesis, molecular docking, and dynamic studies of novel thiazole derivatives incorporating benzimidazole moiety and assessment as antibacterial agents

“…shown a wide variety of biological activities such as anti-cancer [7][8][9], anti-bacterial [10][11], anti-fungal [12][13], anti-viral [14] anti-diabetic [15], anti-in ammatory [16,17] have others found application as liquid crystals [18], and used in cosmetic sunscreens [19], also used as anti-tubercular-agents [20], anticonvulsions [21] and also used as CDK2 inhibitors [22].…”