A vitamin D C/D ring-derived compound with cytotoxicity

Discovery of Cytotoxic Truncated Vitamin D Derivatives Against Both Bortezomib‐Sensitive and Resistant Multiple Myeloma Phenotypes

“…However, the synthetic studies on C/D rings building block is still limited in terms of cancer therapy. Our recently developed VDF-1 displayed comparable cytotoxicity to VD2 against cervical cancer (HeLa cells), non-small cells lung cancer (A549 cells), and MM (KMS-12-PE cells) [17].…”

“…In continuation of our endeavors to find out new antileukemic [12][13][14][15][16] and especially anti MM compounds [9,17], we present the current study revealing an extensive structure activity relationship (SAR) of compound VDF-1 (Fig. 1) [17].…”

“…4c). VDF-1 is known to have an activity to kill lung cancer cells by 6 h incubation, although effect of well-known cytotoxic compound staurosporine is not seen in this condition [17]. We next examined viability of KMS-11 and KMS-11/BTZ cells incubated with VDF-4 for shorter time.…”

“…1) [29]. Concomitantly, some C/D rings derivatives were cytotoxic without triggering hypercalcemia [17,30]. Although Inhoffen-Lythgoe diol itself was inactive, esterification of its primary terminal alcohol produced cytotoxic derivatives against glioma and colorectal adenocarcinoma [30].…”

Vitamin D as a drug: new therapeutic approaches

“…Increasing evidence suggests that vitamin D and its derivatives exhibit antitumor effects in mice (Aslam et al 2021;Li et al 2021) and humans (Wang et al 2021b) and decrease the proliferation of cancer cells derived from several tissues (Hassan et al 2022). Moreover, the expression of VDRs rises with malignant transformation and declines with advanced tumour growth, and activation of these receptors stimulates more than 60 genes, leading to pro-differentiating, anti-proliferative, and anti-metastatic effects on cells (Kim et al 2012).…”