Dependence of the anticancer activity of 1,3‐oxazole derivatives on the donor/acceptor nature of his substitues

Abstract

A series of new 1,3‐oxazole derivatives, containing in position 5 both donor and acceptor substituents were synthesized. These substances were considered as potentially active anticancer pharmacophores in the human tumor cell line panel derived from nine cancer types, including lung, colon, melanoma, renal, ovarian, brain, leukemia, breast, and prostate. Primary in vitro one‐dose anticancer screening was shown that compounds with acceptor substituents (such as –C(O)OMe, –CN) in the position 5 inhibit the growth of most cell lines, and compounds with donor substituents (such as –NHR, −SR) in the position 5 do not practically inhibit the growth of cancer cell lines. It can be assumed that the pharmacological activity of 1,3‐oxazole derivatives depends on donor/acceptor nature of the substituents in position 5. It was proposed to evaluate the donor/acceptor ability of 1,3‐oxazole derivatives using the special parameter φ0, which takes into account the relative position of the boundary levels (HOMO end LUMO). The quantum‐chemical modeling was performed; the special parameter φ0 for 1,3‐oxazole derivatives correlates with the experimental results. Quantum‐chemical calculations of the special parameter φ0 allow modeling the pharmacological activity of 1,3‐oxazole derivatives by introducing donor or acceptor substituents at position 2 or 5. This work may be useful for chemists to develop a target synthesis of potential biologically active compounds.

In silico binding affinity studies of phenyl-substituted 1,3-oxazoles with protein molecules

“…Typically, electron accepting groups at the 4 th position of 1,3-oxazoles increase the stability of the 5-membered electron-rich oxazole cycle. Moreover, oxazole derivatives containing similar substituents have demonstrated high biological activity [9]. The dimethyl substituted oxazole 1 was chosen as a reference molecule; the one-and two-phenyl substituted derivatives 2-4 were compared to oxazole 1.…”

“…The substituted 1,3-oxazoles with branched -conjugated systems also were studied in vitro at the National Cancer Institute in the USA, as part of a therapeutic program for the development of DTP. It was found that these compounds are promising component in the development of new biologically active substances exhibiting antitumor activity which is strongly dependent on the nature of the substituents in heterocyclic core [7][8][9][10]. That leads to additional research activity toward developing new pharmaceuticals [11][12].…”

“…At the same time, the introduction of substituents with a conjugated -electron system in the 1,3-oxazole ring increases the stabilization of resulted complex [Pharm-BioM] by -stacking interaction. The presence of the phenyl substituent in 1,3-oxazole substrate increases biological activity, particularly, the inhibitory effect on the cancerous tumors [9][10]. These molecular fragments can generate an additional complementary structure with many biopolymers, which is considered an important condition for increasing selectivity for potential targets.…”

Anticancer activity of benzoxazole derivative (2015 onwards): a review

“…Hence, molecular docking was done onto the active site of DNA Topo II enzyme (PDB: 3QX3) to understand the antitumor activity of these compounds. Benzoxazole-isoxazole-1,2,3-triazole derivative 1,2,3-Triazole [56,57] and oxazole [57,58] are previously reported to have shown cytotoxic activity. Dadmal [59] and team have coupled this 1,2,3-triazole and oxazole moiety with benzothiazole and benzoxazole moiety (Fig.…”

Influence of Donor and Acceptor Substituents in 1,3-Oxazole Derivatives and Their Anti-Cancer Activity

“…All the selected compounds were evaluated for their anticancer activity. Primary in vitro one dose anticancer assay was performed in full NCI 60 cell panel representing leukemia, non-small cell lung cancer, melanoma and cancers of colon, brain, breast, ovary and prostate in accordance with the protocol of the NCI, USA [7,10]. The compounds were added at a single concentration (10-5M).…”