Tetrasubstituted 2-acetylthiophene derivative 5 was synthesized and then condensed with various nitrogen nucleophiles such as 5-amino-1,2,4-triazole, 2-aminobenzimidazole, aniline or p-chloroaniline to afford the corresponding iminothiophene derivatives 6–8a,b. Condensation of thiophene 5 with malononitrile as carbon nucleophile afforded compound 9, which underwent nucleophilic addition with DMF-DMA to afford compound 10. The newly synthesized products were characterized by elemental analysis, IR, MS, ¹H-¹³C-NMR and CHN analysis and then evaluated for their antimicrobial activity. Results of the in vitro antibacterial activity showed that thiophene derivative 7 was found to be more potent than the standard drug gentamicin against Pseudomonas aeruginosa. Some of these compounds showed potential antimicrobial activities. Molecular docking and Osiris/Molinspiration analyses show the crucial role and impact of substituents on bioactivity and indicate the unfavorable structural parameters in actual drug design: more substitution with electronic donor group doesn’t guarantee more effective bioactivity. This study should greatly help in an intelligent and a controlled pharmacomodulation of antibiotics.

The new coronavirus SARS-COV-2, which emerged in late 2019 from Wuhan city of China was regarded as causing agent of the COVID-19 pandemic. The primary protease which is also known by various synonymous i.e., main protease, 3-Chymotrypsin-like protease (3CL^PRO) has a vital role in the replication of the virus, which can be used as a potential drug target. The current study aimed to identify novel phytochemical therapeutics for 3CL^PRO by machine learning-based virtual screening. A total of 4,000 phytochemicals were collected from deep literature surveys and various other sources. The 2D structures of these phytochemicals were retrieved from the PubChem database, and with the use of a molecular operating environment, 2D descriptors were calculated. Machine learning-based virtual screening was performed to predict the active phytochemicals against the SARS-CoV-2 3CL^PRO. Random forest achieved 98% accuracy on the train and test set among the different machine learning algorithms. Random forest model was used to screen 4,000 phytochemicals which leads to the identification of 26 inhibitors against the 3CL^PRO. These hits were then docked into the active site of 3CL^PRO. Based on docking scores and protein-ligand interactions, MD simulations have been performed using 100 ns for the top 5 novel inhibitors, ivermectin, and the APO state of 3CL^PRO. The post-dynamic analysis i.e,. Root means square deviation (RMSD), Root mean square fluctuation analysis (RMSF), and MM-GBSA analysis reveal that our newly identified phytochemicals form significant interactions in the binding pocket of 3CL^PRO and form stable complexes, indicating that these phytochemicals could be used as potential antagonists for SARS-COV-2.

Cancer therapies are associated with various challenges including the emergence of multidrug resistant tumors, toxicological issues, severe side effects, and economic burden. To counteract these effects, natural products as substitutes and adjuvant therapies have received considerable attention owing to their safety, efficacy, and economic aspects. Various preclinical and clinical studies revealed that natural products and their combinations with chemotherapeutics mediate their anticancer effects via modulation of various signaling pathways implicated in promoting apoptosis, inhibiting excessive cellular proliferation, and mobilizing the immune system. Several lead phytochemicals including curcumin, resveratrol, quercetin, and cannabinoids synergistically act with cancer chemotherapeutics reducing cell proliferation and inducing apoptosis and cell cycle arrest. However, clinical studies on the subject matter are limited and need further extensive studies. It has been observed that patients undergoing chemotherapy use alternative therapies to ameliorate the symptoms associated with the use of chemotherapeutic agents. Nevertheless, some of the patients inform their physicians regarding herbal medicine during chemotherapy while others do not, and even most of the patients do not know the composition of herbal medicine they consume during chemotherapy. Herbal interactions with chemotherapeutics are associated with both beneficial and harmful aspects, but the beneficial aspect overweighs the harmful ones in terms of controlling the symptoms associated with the chemotherapy. Nonetheless, a large number of herbal medicines have been demonstrated to have synergistic effect with chemotherapy and alleviate the side effects of chemotherapeutic agents. The concomitant use of the majority of herbal medicines with chemotherapy has been demonstrated to be beneficial in multiple malignant tumors like cancer of blood, lungs, kidneys, liver, skin, and gastrointestinal tract. However, herbal medicines which possess positive interaction and improve the quality of life of patients should be sorted out and integrated with the chemotherapy. There should be a quality control system for the appraisal of herbal medicine, and there should also be an appropriate system of patient-doctor communication to counsel the patients regarding the beneficial and deleterious effects of the herbal medicine in combination with chemotherapy.

The main aims of this investigation were the isolation of dimeric naphthoquinones, a new class of dinaphthodiospyrols (1–7), from chloroform fractions and screening them for antibacterial, antifungal, and antioxidant potential. The susceptibility of the isolated compounds, namely, dinaphthodiospyrol A (1), dinaphthodiospyrol B (2), dinaphthodiospyrol C (3), dinaphthodiospyrol D (4), dinaphthodiospyrol E (5), dinaphthodiospyrol F (6), and dinaphthodiospyrol G (7) was assessed for antibacterial potential using well diffusion methods. The isolated compounds showed excellent antibacterial activity against selected bacterial strains, including Gram-positive Bacillus subtilis, Streptococcus epidermis, and Bacillus subtilis, and Gram-negative bacteria Klebsiella pneumonia with the zones of inhibition 6 to 26 nm. The standard drug Imipenem showed a maximum inhibitory zone 30 to 35 nm. Similarly, the isolated compounds were screened for antifungal properties, which showed an excellent reduction in the growth of selected fungal strain including Candida albicans, Aspergillus flavus, Fusarium solani, Trichyton logifusus, Microsporum canis, andCandida glabrata. Among all the screened compounds, 7 exhibited good activity (30–49 mm), followed by compounds 5 and 6, (35–46 mm), while compounds 1–4 showed a moderate effect (8–28 mm) against the selected fungal strain against miconazole which showed potent effects (101–110.98 mm). The isolated compounds were also screened for 1, 1-diphenyl-2-picrylhydrazyl (DPPH) activity. In vitro-based free radical was employed using ascorbic acid as a standard antioxidant. The tested compounds (1–7) exhibited significant antioxidant activity in a concentration-dependent manner. The dinaphthodiospyrol 7 exhibited 97.32% scavenging activity, followed by dinaphthodiospyrol 6, 92.01%, and compounds 5 and 4 with 89.90 and 88.43% scavenging activity at 100 μg/mL, respectively; ascorbic acid showed 96.45% scavenging effect. Furthermore, docking analysis was performed to know the exact binding mode of the tetra-substituted derivatives of dinaphthodiospyrols to the selected target proteins. From the docking analysis, it was found that the docking results are well correlated with the experimental observations. In conclusion, the dinaphthodiospyrols exhibited excellent antibacterial, antifungal, and free radical scavenging potential.

Introduction: Monkeypox is a zoonotic disease caused by brick-shaped enveloped monkeypox (Mpox) virus that belongs to the family of ancient viruses known as Poxviridae. Subsequently, the viruses have been reported in various countries. The virus is transmitted by respiratory droplets, skin lesions, and infected body fluids. The infected patients experience fluid-filled blisters, maculopapular rash, myalgia, and fever. Due to the lack of effective drugs or vaccines, there is a need to identify the most potent and effective drugs to reduce the spread of monkeypox. The current study aimed to use computational methods to quickly identify potentially effective drugs against the Mpox virus.Methods: In our study, the Mpox protein thymidylate kinase (A48R) was targeted because it is a unique drug target. We screened a library of 9000 FDA-approved compounds of the DrugBank database by using various in silico approaches, such as molecular docking and molecular dynamic (MD) simulation.Results: Based on docking score and interaction analysis, compounds DB12380, DB13276, DB13276, DB11740, DB14675, DB11978, DB08526, DB06573, DB15796, DB08223, DB11736, DB16250, and DB16335 were predicted as the most potent. To examine the dynamic behavior and stability of the docked complexes, three compounds—DB16335, DB15796, and DB16250 —along with the Apo state were simulated for 300ns. The results revealed that compound DB16335 revealed the best docking score (-9.57 kcal/mol) against the Mpox protein thymidylate kinase.Discussion: Additionally, during the 300 ns MD simulation period, thymidylate kinase DB16335 showed great stability. Further, in vitro and in vivo study is recommended for the final predicted compounds.