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The incorporation of natural products into a suitable delivery system has the potential to augment their therapeutic effectiveness significantly. In this study, we demonstrate how silicasomes, a lipid‐coated mesoporous silica nanorods, influence the anticancer potency and release behaviour of the natural product. Piperlongumine (Pip), a natural product isolated from long pepper, is loaded into mesoporous silica nanorods (MSNRs) followed by a bilayer coating made of 1,2‐Dimyristoyl‐sn‐glycero‐3‐phosphocholine (DMPC). The size and morphology of Pip‐loaded MSNRs (Pip@MSNRs) and phospholipid‐coated Pip@MSNRs (PL‐Pip@MSNRs) are characterized well using suitable analytical techniques. The release of Pip from Pip@MSNRs attained saturation at 48 h while PL‐Pip@MSNRs exhibited the same only after 100 h in both simulated physiological and endolysosomal acidic environments. Moreover, PL‐Pip@MSNRs displayed a higher percentage of Pip release in an acidic medium than in a physiological medium after 24 h. These results confirm that the DMPC coating could assist the pH‐responsive and sustained release of loaded drug from silica nanorods. Most importantly, PL‐Pip@MSNRs demonstrate a higher potency of cytotoxicity and apoptosis against MCF‐7 (Human Breast Carcinoma) cells than the Pip@MSNRs, emphasizing the significance of DMPC‐coated MSNRs as a suitable nanocarrier for natural product delivery. [ABSTRACT FROM AUTHOR]

Transamidation of weakly nucleophilic aromatic amines is achieved under melt conditions and in absence of catalyst, activating agent, base, and solvent. Chemoselectivity of the protocol is demonstrated with transamidation of aniline‐bearing protic carboxylic acid group and wide range of anilines. Broad applicability of the process is demonstrated with the synthesis of bioactive natural product amide, Avenanthranamide‐A. By‐product was isolated for re‐use in synthesis of starting amide, manifests atom economy, and sustainability of the protocol. Thus, our findings imply that the developed protocol is environmentally benign, operationally simple yet versatile for protection‐deprotection free synthesis of amides, peptides and amide‐based drugs. [ABSTRACT FROM AUTHOR]

Piperlongumine, an anticancer natural product, was sequentially demethylated to obtain mono, di and trihydroxy piperlongumines. The hydroxy piperlongumines were evaluated for cytotoxic effect on five human cancer cell lines (kidney, skin, cervical, breast, and lung) in vitro. Results from cytotoxic and cell growth inhibition studies showed monohydroxy piperlongumine (MHPL) was the most active of the series, exhibited potent cytotoxic effect on all the tested cell lines. Flow cytometry analysis shows MHPL inhibited cell cycle progression of HeLa cells in the S phase, indicated that it inhibits the DNA replication process. Fluorescence staining indicated MHPL treated cells were apoptotic. MHPL upregulated the apoptotic genes (caspase‐3, −8, Bax, and p53) and downregulated anti‐apoptotic gene (Bcl‐2). The antioxidant study revealed that hydroxy piperlongumines are effective antioxidants. For MHPL, all the molecular descriptors were within the range of 95 % of approved drugs suggesting high druglikeliness. Our results suggest that MHPL could be developed as a potential lead molecule for cancer therapy. [ABSTRACT FROM AUTHOR]

Amides are indispensable building blocks of biological systems, pharmaceuticals, and materials. We report a highly selective method for the synthesis of amides via transamidation process. Transamidation of N‐acyl‐2‐piperidones with a broad range of amines is demonstrated under exceedingly mild and metal‐free reaction condition that relies on the amide bond twist to weaken the amidic resonance. Transamidation proceeds under the neat condition at room temperature, in short reaction times (30–90 min) with good yields. Considerable variation is tolerated with both amine and imide substrates. Of note, amines bearing carboxylic acids (glycine and serine) and hydroxyl groups (dopamine, tyramine, etc.) are well tolerated which are otherwise problematic under the metal‐catalyzed protocol. Our current method is applicable for transamidation of both alkyl and aryl‐N‐acyl‐2‐piperidones. The practical value of the method is highlighted by the synthesis of four natural product amide alkaloids in high yields under mild reaction conditions. In the absence of nucleophilic amines, N‐acyl‐2‐piperidones undergoes esterification with EtOH at elevated temperature. Single crystal X‐ray analysis of an N‐acyl‐2‐piperidone shows amide bond twist, τ = –20.39° and pyramidalization, χN = –11.73°. This weakens the amidic conjugation and might be the factor controlling the reactivity and selectivity of these imides. We envision that the N‐acyl‐2‐piperidone scaffold would be useful in the synthesis of pharmaceuticals and materials. [ABSTRACT FROM AUTHOR]