An overview of the broad-ranging pharmacological applications of 8-HQ derivatives.

Diarylpyrimidine derivatives (DAPYs) exhibit robust anti-HIV-1 potency, although they have been compromised by E138K variant and severe side-effects and been suffering from poor water solubility. In the present work, hydrophilic morpholine or methylsulfonyl and sulfamide-substituted piperazine/piperidines were introduced into the right wing of DAPYs targeting the solvent-exposed tolerant region I. The anti-HIV-1 activities of 11c (EC 50(WT) = 0.0035 μM, EC 50(E138K) = 0.0075 μM) were the same as and 2-fold better than that of the lead etravirine against the wild-type and E138K mutant HIV-1, respectively, with a relative low cytotoxicity (CC 50 ≥ 173 μM). Further test showed a significant improvement in the water solubility of 11c. Besides, 11c displayed no significant inhibition on main cytochrome P450 enzymes and exhibited no acute/ subacute toxicities at doses of 2000 mg•kg −1 /50 mg•kg −1 in mice. Taken together, we consider that 11c is a promising lead for further structural optimization.

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Although detergent-based decellularization protocols have been widely used to obtain a natural extracellular matrix (ECM) scaffold in tissue engineering, some key challenges still exist. To achieve an optimum natural decellularized scaffold for the construction of tissue-engineered small-diameter blood vessels (TEBV), porcine carotid arteries (PCAs) were decellularized by combining sodium dodecyl sulfate (SDS), sodium deoxycholate (SDC) and Triton X-100 (Triton) in different concentrations. Tissue samples were processed and their histological, biochemical and biomechanical characteristics were investigated. Results showed that only two methods 0.5% (SDS + SDC) and 1% (SDS + SDC) could completely remove of the cellular contents and preserve the native ECM architecture. Furthermore, 1% (SDS + SDC) based methods acquire preferable porosity and suitable mechanical strength. Residual Triton in the ECM scaffold holds intensive cytotoxity. In conclusion, 1%(SDS + SDC) based method can obtain a superior PCAs scaffold for the construction of TEBV. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 619-631, 2018.

The attempts to increase novel drug productivity through creative discovery technologies have fallen short of producing the satisfactory results. For these reasons, evolved from the concept of drug repositioning, "privileged structure"-guided scaffold re-evolution/refining is a primary strategy to identify structurally novel chemotypes by modifying the central core structure and the side-chain of the existing active compounds, or to exploit undescribed bioactivites by making full use of readily derivatized motifs with well-established synthetic protocols. Herein, we review the basic tricks of exploiting privileged structures for scaffold re-evolution/refining. The power of this strategy is exemplified in the discovery of other new therapeutic applications by refining privileged structures in anti-viral agents.

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