Search

A series of 1H-1,2,3 triazole grafted tetrahydro-β-carboline-chalcone/ferrocenylchalcone conjugates were synthesized and in vitro evaluated against estrogen responsive (MCF-7) and triple negative (MDA-MB-231) breast cancer cells. Comparative analysis revealed the improvement of selectivity towards the estrogen responsive cells with the inclusion of a ferrocene core. The most potent compounds of the series were 13l (R = 4-F, n = 3), which exhibited an IC50 value of 10.33 μM against MCF-7 and was ∼5 fold more potent than the standard drug Tamoxifen, while 13d (R = 2,3,4-trimethoxy, n = 5) exhibited an IC50 value of 21.99 μM against the MDA-MB-231 cells, being ∼3 fold more potent than Tamoxifen. The experimental results were further supported by the molecular docking studies in the ligand binding domain of ERα and a greater binding affinity has been attributed to the energetically favourable fit and balance between the hydrophobic and hydrophilic interactions in the ERα active site. [ABSTRACT FROM AUTHOR]

Two exemplary contributions of organometallics in medicinal chemistry, ferroquine and ferrocifen, which exhibit excellent anti-plasmodial and anti-cancer activities, respectively, have opened a new field called medicinal organometallic chemistry. This field has been gaining significant interest due to the recent upsurge in ferrocene-linked organic frameworks with promising biological potential. The success of ferrocene is due to the sustained efforts by organic medicinal chemists and its inherent stability in air, heat and light, low toxicity, low cost and reversible redox properties. The replacement of the aryl/heteroaryl core with a ferrocene nucleus in organic molecules imparts a significant change not only in their molecular properties, such as solubility and hydro-/lipophilicity, but also improves the activities of bioactive compounds. Ferrocifen (ferrocene analogue of hydroxytamoxifen) possesses the remarkable feature of being anti-proliferative against both the MCF-7 (hormone dependent) and MDA-MB-231 (hormone independent) breast cancer cell lines. Accordingly, this review article is aimed at updating researchers on the recent developments (2014–18) on the synthesis and evaluation of ferrocene-containing bio-active pharmacophores with emphasis on their structure–activity relationship and mechanism of action. [ABSTRACT FROM AUTHOR]

A library of 1H-1,2,3-triazole-tethered ospemifene–isatin and ospemifene–spiroisatin conjugates have been synthesized and evaluated for their anti-proliferative activities against MCF-7 and MDA-MB-231 cell lines. The evaluation studies revealed that compound 11j was the most potent with an IC50 value of 1.56 μM against the MCF-7 cell line. Compounds 11k and 11l also displayed a similar trend, with several-fold lower effective concentrations in ER+ cells than in ER− cells. SAR studies revealed that conjugates having a bromo-substituent at the C-5 and C-7 positions of the isatin ring with ethyl/propyl as the spacer were observed to be active with the most potent compound being ∼30 times more potent than Tamoxifen against the MCF-7 cell line. The evaluation results were further supported by docking studies and the stronger binding affinity of the synthesized conjugates was attributed to their greater structural bulk and greater occupation of the ERα active site. [ABSTRACT FROM AUTHOR]

Correction for ‘Ferrocene-appended pharmacophores: an exciting approach for modulating the biological potential of organic scaffolds’ by Amandeep Singh et al., Dalton Trans., 2019, DOI: 10.1039/c8dt03440k. [ABSTRACT FROM AUTHOR]

In pursuit of novel anti-plasmodial agents, a library of triclosan-based dimers both with and without a 1 H -1,2,3 triazole core were designed and synthesized in order to achieve a multitargeted approach. In vitro assessment against chloroquine-susceptible (3D7) and resistant (W2) P. falciparum strains identified that two of the synthesized dimers containing triazole were the most potent in the series. The most potent of the synthesized compounds exhibited IC 50 values of 9.27 and 12.09 μM against the CQ-resistant (W2) and CQ-susceptible (3D7) strains of P. falciparum , with an RI of 0.77, suggesting little or no cross-resistance with CQ. Heme binding and molecular modelling studies revealed the most promising scaffold as a dual inhibitor for hemozoin formation and a P. falciparum chloroquine resistance transporter ( Pf CRT), respectively. In silico studies of the most potent compound revealed that it shows better binding affinity with Pf ACP and Pf CRT compared to TCS. To the best of our knowledge, this is the first report of triclosan-based compounds demonstrating promising heme-inhibition behaviour, with binding values comparable to those of chloroquine (CQ)., Competing Interests: There is no conflict of interest to declare., (This journal is © The Royal Society of Chemistry.)

A series of tetrahydro-β-carboline-isatin conjugates, with varying substituents as well as stereochemistry at C-1 and C-5 position of tetrahydro-β-carboline (THβC) and isatin ring, were prepared and assayed for anti-proliferative efficacy on Estrogen Responsive ER(+) (MCF-7) and ER(-ve) MDA-MB-231 cell-lines. The synthesized scaffolds displayed selective anti-proliferative efficacy against MCF-7 cell-line with the most active conjugate 8b exhibiting an IC 50 value of 37.42 μM, comparable to that of peganumine A, a tetrahydro-β-carboline analogue, isolated from Peganum harmala . The synthesized compound 8b was also more potent than the standard drug tamoxifen (IC 50 = 50 μM against MCF-7). The observed activities were further corroborated via docking studies in ER-α (PDB ID: 3ERT)., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Two exemplary contributions of organometallics in medicinal chemistry, ferroquine and ferrocifen, which exhibit excellent anti-plasmodial and anti-cancer activities, respectively, have opened a new field called medicinal organometallic chemistry. This field has been gaining significant interest due to the recent upsurge in ferrocene-linked organic frameworks with promising biological potential. The success of ferrocene is due to the sustained efforts by organic medicinal chemists and its inherent stability in air, heat and light, low toxicity, low cost and reversible redox properties. The replacement of the aryl/heteroaryl core with a ferrocene nucleus in organic molecules imparts a significant change not only in their molecular properties, such as solubility and hydro-/lipophilicity, but also improves the activities of bioactive compounds. Ferrocifen (ferrocene analogue of hydroxytamoxifen) possesses the remarkable feature of being anti-proliferative against both the MCF-7 (hormone dependent) and MDA-MB-231 (hormone independent) breast cancer cell lines. Accordingly, this review article is aimed at updating researchers on the recent developments (2014-18) on the synthesis and evaluation of ferrocene-containing bio-active pharmacophores with emphasis on their structure-activity relationship and mechanism of action.

Correction for 'Ferrocene-appended pharmacophores: an exciting approach for modulating the biological potential of organic scaffolds' by Amandeep Singh et al., Dalton Trans., 2019, DOI: 10.1039/c8dt03440k.

A diverse range of triazoles were prepared following well established, Cu-mediated azide-alkyne cycloaddition reactions with the aim of probing the anti-tubercular structure-activity relationships (SAR) within the β-lactam-ferrocene-triazole conjugate family. The anti-tubercular evaluation studies of the synthesized conjugates revealed that none of the scaffolds exhibited any activity that restricted mycobacterial growth even at high doses. The introduction of various substituents onto the N-1 of the β-lactam ring, introducing mono- or di-ferrocenylchalcone substituents at the C-3 position as well as introducing a spacer of varying chain length failed to produce any significant enhancement in the activity profiles. The described protocol was a successful attempt on the inclusion of a ferrocene nucleus in the β-lactam family tethered via triazole linkers having metabolic stability and physicochemical favourability.

Twenty different triazoles were prepared to probe the anti-tubercular structure-activity relationships (SAR) within the β-lactam-ferrocene-triazole conjugate family. The compounds have been synthesized by copper-catalyzed "click chemistry". In vitro anti-tubercular activity was determined for each compound but the synthesized hybrids failed to inhibit Mycobacterium tuberculosis growth even at high doses. The manuscript assumes significance as this is the first report on the inclusion of ferrocene nucleus in the well established β-lactam family via triazole linkers with reputed physicochemical profiles.