Synthesis of tetrazole hybridized with thiazole, thiophene or thiadiazole derivatives, molecular modelling and antimicrobial activity.

Background: Tetrazole-based derivatives and their electronic structures have displayed interesting antimicrobial activity. Methods: The tetrazole-based hybrids linked with thiazole, thiophene and thiadiazole ring systems have been synthesized through various chemical reactions. The computational method DFT/B3LYP has been utilized to calculate their electronic properties. The antimicrobial effectiveness was investigated against representative bacterial and fungal strains. Additionally, the synthesized derivatives binding interaction was stimulated by docking program against PDB ID: 4URO as a model of the ATP binding domain of S. aureus DNA Gyrase subunit B. Results: The structures of the synthesized tetrazole-based derivatives were confirmed by IR, NMR, and Mass spectroscopic data. The DFT/B3LYP method showed that the thiadiazole derivatives 9a-c had lower ΔEH-L than the thiophenes 7a-c and thiazoles 5a-c. The hybrids 5b, 5c, and 7b exhibited proper antibacterial activity against Gram's +ve bacterial strains (S. aureus and S. pneumonia), while 9a displayed potent activity towards Gram's -ve bacterial strains (S. typhimurium and E. coli). Meanwhile, derivatives 5a-b, 7a, 7c, and 9c showed good effectiveness towards fungal strain (C. albicans). Conclusion: The study provides valuable tetrazole core-linked heterocyclic rings and opens the door to further research on their electrical characteristics and applications. Tetrazoles and thiazoles have antibacterial properties in pharmacological frameworks, making these hybrids potential lead molecules for drug development. The conclusion summarizes the data and suggests that the synthesized chemicals' interaction with a particular protein domain suggests focused biological activity.

Characterization of aminoglycoside resistance genes in multidrug-resistant Klebsiella pneumoniae collected from tertiary hospitals during the COVID-19 pandemic.

Since the peak of the coronavirus disease 2019 (COVID-19) pandemic, concerns around multidrug-resistant (MDR) bacterial pathogens have increased. This study aimed to characterize aminoglycoside resistance genes in MDR Klebsiella pneumoniae (K. pneumoniae) collected during the COVID-19 pandemic. A total of 220 clinical isolates of gram-negative bacteria were collected from tertiary hospitals in Makkah, Saudi Arabia, between April 2020 and January 2021. The prevalence of K. pneumoniae was 40.5%; of the 89 K. pneumoniae isolates, MDR patterns were found among 51 (57.3%) strains. The MDR isolates showed elevated resistance rates to aminoglycoside agents, including amikacin (100%), gentamicin (98%), and tobramycin (98%). PCR assays detected one or more aminoglycoside genes in 42 (82.3%) MDR K. pneumoniae strains. The rmtD gene was the most predominant gene (66.7%; 34/51), followed by aac(6')-Ib and aph(3')-Ia (45.1%; 23/51). The aac(3)-II gene was the least frequent gene (7.8%; 4/51) produced by our isolates. The rmtC gene was not detected in the studied isolates. Our findings indicated a high risk of MDR bacterial infections through the COVID-19 outbreak. Therefore, there is a need for continuous implementation of effective infection prevention control (IPC) measures to monitor the occurrence of MDR pathogens and the emergence of MDR bacterial infections through the COVID-19 outbreak.

Epidemiological Features of COVID-19 in Makkah City: A Retrospective Data Analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is continuing to circulate and change, affecting billions of people worldwide and leading to increased mortality rates, especially in the Holy City of Makkah, Kingdom of Saudi Arabia (KSA). This study was aimed at investigating the epidemiological features of COVID-19 in Makkah City, KSA. METHODS: A retrospective analysis was conducted to investigate the prevalence of COVID-19 and the association between the severity and mortality of COVID-19 with demographic factors and comorbidities. RESULTS: Among 4,742 COVID-19 patients, the incidence rate observed in males was 66.7%, and 69.7% were from Al-Noor Specialized Hospital. The highest incidence rate (25.2%) was found in the age group > 60 years old, followed by the age group 51-60 years (21.8%). Furthermore, the highest frequency was observed in patients from Saudi Arabia (36.8%), followed by patients from Myanmar (14.7%) and Bangladesh (9.4%). The overall frequency of COVID-19 severity and death was 20.3% and 11.6%, respectively. Body mass index analysis showed that 1% of the patients were underweight, while 9.2% were overweight and 4.4% were obese. In addition, 9.6% had diabetes, 6.9% had hypertension, 1.1% had heart disease, and 2.2% had other chronic diseases. CONCLUSION: The study concluded that the overall percentages of severe COVID-19 (intensive care unit) cases and deaths in Makkah City, KSA, were 20.3% and 11.6%, respectively, and there was a higher incidence in male patients. The severity of infection was shown to have a strong significant correlation with different chronic diseases, nationality, body mass index, death rate (mortality), heart disease, and length of hospital stay (P < 0.05). Despite these findings, more studies are needed to explain the underlying mechanisms that influence the overall health status of patients with specific characteristics and comorbidities.

Virulence and biofilms as promising targets in developing antipathogenic drugs against candidiasis.

Candida albicans has remained the main etiological agent of candidiasis, challenges clinicians with high mortality and morbidity. The emergence of resistance to antifungal drugs, toxicity and lower efficacy have all contributed to an urgent need to develop alternative drugs aiming at novel targets in C. albicans. Targeting the production of virulence factors, which are essential processes for infectious agents, represents an attractive substitute for the development of newer anti-infectives. The present review highlights the recent developments made in the understanding of the pathogenicity of C. albicans. Production of hydrolytic enzymes, morphogenesis and biofilm formation, along with their molecular and metabolic regulation in Candida are discussed with regard to the development of novel antipathogenic drugs against candidiasis.