Serine- and threonine-derived diamine equivalents for site-specific incorporation of platinum centers in peptides, and the anticancer potential of these conjugates

Kumbhakonam, Sateeshkumar; Vellaisamy, Kasipandi; Saroj, Soumya; Venkatesan, Nalini; Karunagaran, Devarajan; Manheri, Muraleedharan K.

doi:10.1039/c7nj03999a

Cited by 4 publications

(2 citation statements)

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“…Another approach that has gained prominence is pharmacophore hybridization which could give a much better control on drug distribution and pharmacodynamics [14–17] . Here, individual drugs may either be conjugated through a spacer or their key pharmacophoric features integrated into a single chemical framework to achieve multi‐targeting [16,18–23] . Possible number of drug/pharmacophore combinations is quite large but logical selection of targets/pathways for co‐targeting is important to get the best therapeutic outcome.…”

Section: Introductionmentioning

confidence: 99%

“…[14][15][16][17] Here, individual drugs may either be conjugated through a spacer or their key pharmacophoric features integrated into a single chemical framework to achieve multi-targeting. [16,[18][19][20][21][22][23] Possible number of drug/pharmacophore combinations is quite large but logical selection of targets/pathways for co-targeting is important to get the best therapeutic outcome. This may be done through network-based analysis of human protein-protein interactome.…”

Section: Introductionmentioning

confidence: 99%

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Hybridization of the Pharmacophoric Features of Discoipyrrole C and Combretastatin A‐4 toward New Anticancer Leads

Kurian,

Ashtam,

Kesavan

et al. 2023

ChemMedChem

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Pharmacophore hybridization is an attractive strategy to identify new leads against multifactorial diseases such as cancer. Based on literature analysis of compounds possessing ‘vicinal diaryl’ fragment in their structure, we considered Discoipyrroles A−D and Combretastatin A‐4 (CA‐4) as possible components in hybrid design. Discoipyrrole C (Dis C) and CA‐4 were used as reference compounds in these studies and their hybrids, in the form of 4,5‐diaryl‐1H‐pyrrol‐3(2H)‐ones, were synthesized from suitable amino acid precursors though their ynone intermediates. Of these, the hybrid having exact substitution pattern as that of CA‐4 showed better potency and selectivity than Dis C, but its activity was less compared to CA‐4. This new analog disrupted interphase microtubules by inhibiting tubulin assembly by binding to the colchicine site, induced multipolar spindles, caused cell cycle block and apoptosis in HeLa cells. It also inhibited colony formation and migration of breast cancer cell lines.

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Section: Introductionmentioning

confidence: 99%