Microwave Irradiated Synthesis of Pyrimidine Containing, Thiazolidin-4-ones: Antimicrobial, Anti-tuberculosis, Antimalarial, and Anti-protozoa evaluation

Aim: This study aims to synthesize thiazolidine-4-one compounds with a pyrimidine nucleus and evaluate against different species of bacteria, fungi, protozoa, and the malaria parasite. Background: Microwave irradiation was the best method for synthesizing the thiazolidin-4-one ring system. It took only 15 minutes for synthesizing thiazolidin-4-one while the conventional method required 12 hours. The rapid reaction was the main concern of this research. Objective: Pyrimidine and Thiazolidin-4-one nucleus have broad-spectrum biological activity and when it is introduced with other hetero atoms containing moiety, many types of biological activities have been found; antimicrobial, anti-tuberculosis, anti-protozoa, antimalarial are the main activities. The activity of these compounds inspired us to do extra research on Thiazolidin-4-one fused pyrimidines with different functional groups. The aim of this is to synthesize a combination of these two ring systems in less time by using a microwave irradiation method and to evaluate new compounds for different bioactivity. Method: 2-(4-Chlorophenyl)-3-(4-(substituted phenyl)-6-(substituted aryl) pyrimidin-2-yl) thiazolidin-4-ones (6A-J) were synthesized by microwave irradiation to save energy and time. The structure of all newly synthesized motifs was characterized by spectral analysis (1H NMR, 13C NMR, IR, spectroscopy) and screened for antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes, antifungal activity against Candida albicans, Aspergillus niger, Aspergillus clavatus, anti-tuberculosis activity against M. tuberculosis H37RV, antimalarial activity against Plasmodium falciparum and anti-protozoa activity against L. mexicana and T. cruzi. Result: Because of microwave irradiation synthesis, time period is very less for preparing the new compound. Biological response given by compounds 6B, 6C, 6D, 6E, 6G, 6H, and 6J was found excellent. Conclusion: Good yield with purity of the newly synthesized thiazolidine-4-one compounds obtained in less time by using microwave irradiation. The biological response of some of the compounds of this series was found excellent

Beta-lactam antibiotics as reserve medications for the treatment of drug-resistant tuberculosis

The review article presents an analysis of literature data on the necessity to expand the range of medications possessing anti-tuberculosis activity for the treatment of the most severe forms of drug-resistant tuberculosis through the use of beta-lactam antibiotics in chemotherapy regimens. The mechanism of action of beta- lactam antibiotics on mycobacterium tuberculosis is shown, and the results of in vitro studies to assess their anti-tuberculosis activity are presented. Clinical studies on the use of carbapenems prove the feasibility of their use for the treatment of patients with tuberculosis with multiple and extensive drug resistance of the pathogen.

In vitro and in vivo activity of oxazolidinone candidate OTB-658 against Mycobacterium tuberculosis

In this work, we assess anti-tuberculosis activity of OTB-658 in vitro and in vivo . In vitro , OTB-658 showed bacteriostatic effectiveness with a lower minimum inhibitory concentration than linezolid against Mycobacterium tuberculosis . The minimal bactericidal concentrations and time-kill curves for OTB-658 indicated similar inhibition activity to that of linezolid. OTB-658 entered macrophages to inhibit of M. tuberculosis growth. OTB-658 had a low mutant frequency (10 −8 ), which would prevent drug-resistant mutations from emerging in combination regimens. In vivo , OTB-658 reduced colony-forming unit counts in the lungs and slightly inhibited bacterial growth in the spleen in the early stage and steady state in acute and chronic murine TB models. These results support the preclinical evaluation of OTB-658 and further clinical trials in China.

Potensi Ekstrak Curcuma Xanthorrhiza Sebagai Terapi Pendamping Tuberkulosis

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis. Most of it attacks the lungs and is still a world health problem. Therapy with a combination of drugs called Anti-Tuberculosis Drugs (OAT) has become a standard and effective cure for TB sufferers as long as it is regular and complete. However, the drawback of OAT is that it has several side effects that allow temporary drug interruption and worsening of clinical manifestations. For that we need companion therapy to overcome this. The purpose of this paper is to search and analyze literature regarding the potential of Curcuma xanthorrhizol extract as a companion therapy for tuberculosis. The method used is by searching the pubmed and google scholar databases with the keywords curcuma xanthorrhiza, curcumin, xanthorrhizol, flavonoids, Mycobacterium tuberculosis, anti-inflammatory, anti-oxidant, gastroprotective and anti-bacterial. Then the literature is selected based on inclusion and exclusion criteria. The results and discussion obtained were that curcuma xanthorrhiza has various active compounds that are useful for preventing side effects of OAT such as curcumin, xanthorrhizol, and flavonoids. Curcuma xanthorrhiza can be used as anti-inflammatory, anti-oxidant, gastroprotective so that side effects such as skin rashes, nausea, vomiting, abdominal pain and others can be prevented. Besides that, curcumin content in Curcuma xanthorrhiza has anti-tuberculosis activity. The conclusion is that curcuma xanthorrhiza extract can be considered as a companion drug for TB patients. It can be done further research on the potential of ginger

Screening of Compounds for Anti-tuberculosis Activity, and in vitro and in vivo Evaluation of Potential Candidates

Tuberculosis (TB) is a debilitating infectious disease responsible for more than one million deaths per year. The emergence of drug-resistant TB poses an urgent need for the development of new anti-TB drugs. In this study, we screened a library of over 4,000 small molecules and found that orbifloxacin and the peptide AK15 possess significant bactericidal activity against Mycobacterium tuberculosis (Mtb) in vitro. Orbifloxacin also showed an effective ability on the clearance of intracellular Mtb and protect mice from a strong inflammatory response but not AK15. Moreover, we identified 17 nucleotide mutations responsible for orbifloxacin resistance by whole-genome sequencing. A critical point mutation (D94G) of the DNA gyrase (gyrA) gene was found to be the key role of resistance to orbifloxacin. The computational docking revealed that GyrA D94G point mutation can disrupt the orbifloxacin–protein gyrase interactions mediated by magnesium ion bridge. Overall, this study indicated the potential ability of orbifloxacin as an anti-tuberculosis drug, which can be used either alone or in combination with first-line antibiotics to achieve more effective therapy on TB.

Phytochemical Analysis and Anti-Tuberculosis Activity of Extracts of Detarium senegalense Bark and Root

Tuberculosis [TB] remains one of the major global health threats leading to morbidity and mortality. Detarium senegalense J. F. Gmelin belongs to a group of medicinal plants that are used by traditional medicine healers for the treatment of venereal diseases, urogenital infections, hemorrhoids, rheumatism, stomach-ache, intestinal worms, diarrhea, bronchitis, tuberculosis, convulsion, malaria and leprosy. The present study was aimed to investigate the in vitro anti-tuberculosis effect of different solvent extracts of Detarium senegalense bark and root against attenuated strain of Mycobacterium bovis [BCG]. The crude extracts [n-hexane, ethyl-acetate, methanol] of the plant parts were successively extracted and tested in vitro by broth microdilution technique against M. bovis. The result shows that the crude extracts inhibited the growth of M. bovis at concentrations ranging from 7.8 – 250 μg/mL. The ethyl-acetate extract of Detarium Senegalense bark was the most effective in inhibiting the growth of M. bovis with a minimum inhibitory concentration [MIC] of 7.8 µg/mL while the ethyl-acetate and methanol extract of the plant’s root had MICs of 250 µg/mL. This study demonstrates the efficacy of extracts of Detarium senegalense bark and root as potential agents in the management of the tuberculosis disease.