A field‐based disparity analysis of new 1,2,5‐oxadiazole derivatives endowed with antiproliferative activity

Abstract

A series of 1,2,5-oxadiazoles was synthesized as new potential antiproliferative agents. The in vitro cytotoxic activity evaluation of title compounds through MTT-assay revealed that some of them showed significant activity against the HCT-116 cancer cell line. The field-based disparity analysis provided indications about the electrostatic, hydrophobic and shape features underlying the cytotoxicity, suggesting that increasing the negative electrostatic field on the heterocyclic core of the structure has positive effects on the activity. The structure-activity relationships (SAR) around a particular compound can be explained allowing for a structural rationale for the differences in activity. The SAR provided by this series of compounds can be exploited to carry out further lead optimization. This article is protected by copyright. All rights reserved

Structural Biology of STAT3 and Its Implications for Anticancer Therapies Development

“…A list of papers published in the last five years, together with a summary, is reported in Table 2 . Multiple strategies, involving different protein regions, have been followed aiming to design potent and selective inhibitors of the STAT3 functions [ 59 , 60 , 61 , 62 ].…”

Exploring the Biological Activity of a Library of 1,2,5-Oxadiazole Derivatives Endowed With Antiproliferative Activity

“…Interestingly, some derivatives were able to exert a significant antiproliferative effect, with IC 50 values below 20 μM (6, 19 and 29), on both HCT-116 and HeLa cell lines. These results suggest a crucial role for the concurrent insertion of CF 3 and Cl groups in position meta and para of the phenyl rings. Moreover, the IC 50 values reported in Table I highlight a detrimental role in the biological activity for the ortho position, as a notable increase was observed for derivatives 5 and 18.…”

“…Chemistry. In this section, the synthetic procedures ( Figure 2) to obtain the new products (14-17, 24-26 and 28) are reported; the remaining compounds were obtained through previously reported methods (3). Briefly, the key intermediates 30a-c, synthesized from the properly substituted chlorobenzaldehydes following a multi-step procedure (4), led to the final products 15, 16 and 26, through a coupling reaction with the suitable acyl chlorides.…”

“…With the aim of identifying novel potential chemotherapeutic agents (3)(4)(5)(6)(7)(8)(9), we synthesized a small library of 1,2,5-oxadiazole derivatives (3) ( Figure 1) related to MD77, previously disclosed by our research group (4), as an interesting anti-proliferative hit. Some derivatives had already been tested on HCT-116 cell line and showed a significant activity.…”

“…Some derivatives had already been tested on HCT-116 cell line and showed a significant activity. Therefore, to complete our studies on this interesting scaffold, several new derivatives (3) (Figure 2) were designed and synthesized, following a synthetic procedure reported in literature (3). Their cytotoxicity towards the HCT-116 cell line, evaluated by MTT assay, indicated that some members of the library exert growth inhibition properties.…”