Pharmacophore-based, rationale design, and efficient synthesis of novel tetrahydrobenzo[b]thiophene candidates as potential dual Topo I/II inhibitors and DNA intercalators.

A series of tetrahydrobenzo[b]thiophene derivatives was designed and synthesized as dual topoisomerase (Topo) I/II inhibitors implicating potential DNA intercalation. Ethyl-2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene-4-carboxylate (1) was prepared by modification of the Gewald reaction procedure using a Fe2O3 nanocatalyst and then it was used as a building block for the synthesis of tetrahydrobenzo[b]thiophene candidates (2-14). Interestingly, compound 14 showed the best cytotoxic potential against hepatocellular, colorectal, and breast cancer cell lines (IC50 = 7.79, 8.10, and 3.53 µM), respectively, surpassing doxorubicin at breast cancer (IC50 = 4.17 µM). Meanwhile, the Topo I and II inhibition assay displayed that compound 3 could exhibit the best inhibitory potential among the investigated candidates (IC50 = 25.26 and 10.01 nM), respectively, in comparison to camptothecin (IC50 = 28.34 nM) and doxorubicin (IC50 = 11.01 nM), as reference standards. In addition, the DNA intercalation assay showed that compound 14 could display the best binding affinity with an IC50 value of 77.82 µM in comparison to doxorubicin (IC50 = 58.03 µM). Furthermore, cell cycle and apoptosis analyses described that compound 3 prompts the G1 phase arrest in michigan cancer foundation-7 cancer cells and increases the apoptosis ratio by 29.31% with respect to untreated cells (2.25%). Additionally, the conducted molecular docking assured the promising binding of the investigated members toward Topo I and II with potential DNA intercalation. Accordingly, the synthesized compounds could be treated as promising anticancer candidates for future optimization.

High versus low dose oral isotretinoin in the treatment of cutaneous and genital warts.

Although oral isotretinoin has been considered as a potential therapeutic option for the treatment of different types of warts, the optimum dosage regimen is not yet well-established. To evaluate the efficacy and adverse effects of high versus low doses of oral isotretinoin in the treatment of cutaneous and genital warts. The study included 100 patients who were randomly assigned to two groups, 50 patients in each. Group 1 received 0.6 mg/kg/day (high dose isotretinoin) and Group 2 received 0.3 mg/kg/day (low dose isotretinoin). In both groups, therapy was given daily until resolution was achieved or for a maximum of 3 months. Complete clearance of warts was observed in 76% of the high dose isotretinoin group and in 46% of the low dose isotretinoin group. There was a statistically significant difference in the therapeutic response between the two groups. Recurrence was higher in the low dose group (26%) than the high dose group (7.8%). Adverse effects were mild and tolerable. High dose of systemic isotretinoin is more effective than low dose and seems to be a promising well-tolerated and effective therapeutic option for the treatment of cutaneous and genital warts.

Treatment of recalcitrant warts with intralesional measles, mumps, and rubella vaccine: a promising approach.

BACKGROUND: Recalcitrant warts represent a frustrating challenge for both patients and physicians. Although many destructive and immunotherapeutic modalities are available for the treatment of warts, an ideal, universally effective approach has not been explored to date. Recently, intralesional antigen immunotherapy has shown promising efficacy in the treatment of warts. The aim of the study was to evaluate the efficacy and safety of intralesional measles, mumps, and rubella (MMR) vaccine in the treatment of recalcitrant warts. METHODS: The study included 70 adult patients with multiple recalcitrant extragenital warts of different sizes and durations, with or without distant warts. They were directly injected, without a pre-sensitization skin test, with 0.3 intralesional MMR vaccine into the largest wart at 2-week intervals until complete clearance or for a maximum of five treatments. Follow-up was made every month for six months to detect any recurrence. RESULTS: Sixty-five patients, 35 men and 30 women, completed the study, and five patients discontinued for various reasons. Complete clearance of the lesions was observed in 41 patients (63%), partial response in 15 patients (23%), and no response in nine patients (14%). Complete response was demonstrated in 74.5% of those presenting with distant warts. Side effects were mild and insignificant in the form of pain during injection, itching, erythema, and edema at the site of injection and flu-like symptoms. Recurrence was detected in two patients only. CONCLUSIONS: Intralesional immunotherapy by MMR vaccine is a promising, effective, and safe treatment modality for recalcitrant warts.