Antituberculosis Drugs Research Articles

Structure-based design and synthesis of (E)-l-(s-pheny1)-N-(4-(2,2,4-trimethy1-2,3-dihydro-lH-benzo[b][l,4]diazepin-l-yl)phenyl)methanimine motifs as antimicrobial and anti-tubercular agents

Benzodiazepines' chemistry and synthesis as heterocyclic compounds have recently attracted a lot of attention, due to their extensive biological diversity in drug design and potential for usage in agrochemicals. Eco-friendly and highly efficient method was herein reported for the synthesis of a new series of Schiff base of benzodiazepine derivatives 3a-l using microwave-assisted approach. Firstly, 2,2,4-trimethy1-2,3-dihydro-lH-benzo[b][l,4]diazepine (1) was synthesized by AgNO3-catalyzed reaction of o-phenylenediamine with excess of acetone. Coupling of benzodiazepine 1 with 4-chloroaniline afforded intermediate benzodiazepine 2 which was subsequently reacted with benzaldehyde derivatives via microwave irradiation technique to access twelve final targeted benzodiazepine Schiff bases, 3a-l. The chemical structures of the scaffolds 3a-l were authenticated using analytical and spectroscopic data. Benzodiazepine Schiff bases 3a-l were investigated for their in vitro antimicrobial activities using Agar diffusion technique and screened for their minimum inhibitory concentration (MIC) using microtube dilution technique. Ten pathogenic organisms comprising of seven bacterial and three fungal isolates were utilized for the screening. Ciprofloxacin was the positive control for antibacterial screening while fluconazole was engaged as the positive control for the antifungal screening. The most efficacious antimicrobial agent among the series was (E)-l-(2-Chloropheny1)-N-(4-(2,2,4-trimethyl-2,3-dihydro-lH-benzo[b][l,4] diazepinlyl)phenyl)methanimi ne (3b) with a MIC value of 3.13 µg/mL and MBC of 6.25 µg/mL among all the synthesized compounds synthesized and screening for antimicrobial assessment. Compound 3b also emerged as the best anti-tubercular agent IC50 of 40 µg/mL against Mycobacterium tuberculosis, Mycobacterium bovis and H37Rv

A Review on Chemistry and Methods of Synthesis of 1,2,4-Triazole Derivatives.

This review provides a comprehensive overview of research on 1,2,4-triazoles conducted over the last fifteen years. 1,2,4-Triazoles are highly significant in the pharmaceutical industry, with numerous compounds from this class used clinically as antifungal, antiviral, antibacterial, anti-inflammatory, and antitubercular agents. Beyond their pharmaceutical relevance, this review also explores their role in material science and agriculture. In material science, 1,2,4-triazoles are gaining prominence, particularly in the development of energetic materials (EMs), due to their exceptional properties such as thermal stability, coordination ability, and performance comparable to well-known explosives. Their applications extend to polymers, corrosion inhibitors, and metal-organic frameworks (MOFs), and they play a significant role in the development of functional materials for sensors, catalysis, and energy storage. Additionally, the review addresses general aspects and synthetic methodologies for the functionalization and construction of the 1,2,4-triazole ring. Synthetic methods discussed include metalation synthesis, cyclization of hydrazine derivatives, multicomponent reactions, cyclization of amides and amidines, and microwave-assisted synthesis. Given the significance of the triazole scaffold, its synthesis has garnered considerable attention due to its wide-ranging applications across various industrial sectors.

Erratum for Prommi et al., "Co-resistance to isoniazid and second-line anti-tuberculosis drugs in isoniazid-resistant tuberculosis at a tertiary care hospital in Thailand".

Erratum for Prommi et al., "Co-resistance to isoniazid and second-line anti-tuberculosis drugs in isoniazid-resistant tuberculosis at a tertiary care hospital in Thailand".

Treatment course of cavitary pulmonary tuberculosis combined with tuberculosis in a parotid Warthin's tumor: a case report and literature review.

Extrapulmonary tuberculosis (TB) is a relatively rare form of tuberculosis infection, accounting for approximately 15% of all tuberculosis infections. Lymph nodes are the most commonly affected sites, while involvement of the parotid gland is extremely rare. We present the case of a 65-year-old male patient with a one-month history of a left parotid mass. The patient has a history of diabetes and long-term smoking, and a chest X-ray revealed secondary fibrotic pulmonary tuberculosis, while sputum smears were culture-negative for Mycobacterium tuberculosis (Mtb). The parotid mass was surgically removed and subjected to routine HE staining, acid-fast staining, and PCR molecular testing for Mtb. The final diagnosis was Warthin's tumor of the parotid gland with concomitant tuberculosis. One month after removal of the parotid mass, the patient's chest CT showed cavitary tuberculosis. Subsequently, the patient received anti-tuberculosis treatment; however, due to severe gastrointestinal adverse effects, the patient stopped the medication in less than a month and did not receive regular treatment. Four months after stopping the medication, the patient's pulmonary tuberculosis progressed and worsened. Combined tuberculosis in Warthin's tumor is extremely rare, with only 14 cases reported to date. However, the specific pathogenesis of this condition is not yet fully understood, and the preliminary treatment and prognosis have not been conclusively determined. Early diagnosis of tuberculosis, standardized and effective use of anti-tuberculosis drugs, and personalized treatment are crucial in the management of tuberculosis. We have reviewed the treatment progress of this rare disease and analyzed the potential pathogenesis of the condition. Furthermore, we have summarized the current understanding of the pathogenesis of tuberculosis, drug resistance mechanisms, and the latest treatment advances. These studies have important clinical implications for better understanding and treating extrapulmonary tuberculosis and tuberculosis within Warthin's tumor of the parotid gland. This comprehensive analysis sheds light on the complexities of tuberculosis and provides valuable insights for improved management and care of affected individuals.

Inhibition mechanism of potential antituberculosis compound lansoprazole sulfide

Tuberculosis is one of the most common causes of death worldwide, with a rapid emergence of multi-drug-resistant strains underscoring the need for new antituberculosis drugs. Recent studies indicate that lansoprazole-a known gastric proton pump inhibitor and its intracellular metabolite, lansoprazole sulfide (LPZS)-are potential antituberculosis compounds. Yet, their inhibitory mechanism and site of action still remain unknown. Here, we combine biochemical, computational, and structural approaches to probe the interaction of LPZS with the respiratory chain supercomplex III2IV2 of Mycobacterium smegmatis, a close homolog of Mycobacterium tuberculosis supercomplex. We show that LPZS binds to the Qo cavity of the mycobacterial supercomplex, inhibiting the quinol substrate oxidation process and the activity of the enzyme. We solve high-resolution (2.6 Å) cryo-electron microscopy (cryo-EM) structures of the supercomplex with bound LPZS that together with microsecond molecular dynamics simulations, directed mutagenesis, and functional assays reveal key interactions that stabilize the inhibitor, but also how mutations can lead to the emergence of drug resistance. Our combined findings reveal an inhibitory mechanism of LPZS and provide a structural basis for drug development against tuberculosis.

Guidelines for diagnosis and management of drug-induced liver injury caused by anti-tuberculosis drugs (2024 version)

Guidelines for diagnosis and management of drug-induced liver injury caused by anti-tuberculosis drugs (2024 version)

Features of the pathogen and efficacy of drug-resistant tuberculosis treatment

According to the World Health Organization (WHO), nearly 10.6 million new cases of tuberculosis were detected in 2022, indicating an increase of 3.5 % from the reported 10.3 million in 2021. After the COVID-19 pandemic, the incidence of tuberculosis increased by 3.9 % from 2020 to 2022. According to the latest regulatory documents, multidrug-resistant pathogen is diagnosed when any bacteriologic or molecular genetic methods reveal drug resistance of M. Tuberculosis complex at least to isoniazid and rifampicin regardless of resistance to other antituberculosis drugs.With a wide range of virulence genes, the tuberculosis pathogen expresses genes in different phases of infection. Some genes are “switched on” in the early phases and are important for overcoming immune defenses and spreading the pathogen in the host, while others are important for survival in the latent phase. These characteristics of Mycobacterium tuberculosis determine the need for correct and adequate selection of therapy. The problem of diagnostics and treatment of drug-resistant tuberculosis remains extremely urgent. Despite the introduction of new tests for rapid determination of drug susceptibility spectrum of Mycobacterium tuberculosis, the problem of timely and adequate prescription of chemotherapy regimen remains. When selecting therapy, the problem of prescribing a combination of antituberculosis drugs with proven efficacy against M. tuberculosis remains. The need to assess the patient’s comorbid status, which affects the effectiveness of treatment and the occurrence of relapses, remains relevant.Despite the introduction of new tests for rapid determination of the drug susceptibility spectrum of Mycobacterium tuberculosis, the problem of timely and adequate prescription of chemotherapy remains relevant. The problem of prescribing a combination of antituberculosis drugs with proven efficacy against M. tuberculosis remains in the selection of therapy. Currently, the introduction of bedaquiline in therapy regimens is important for improving the effectiveness of tuberculosis treatment. In addition, studies are underway to shorten the duration of therapy for MDR-TB and XDR-TB, which is particularly important for maintaining patient adherence to treatment.

Predictive value of systemic immune-inflammatory biomarkers for drug-induced liver injury in hepatitis B virus surface antigen positive tuberculosis patients: A retrospective observational study.

Drug-induced liver injury (DILI) is a major concern in tuberculosis (TB) treatment. For early detection of DILI, immune-inflammatory biomarkers are needed for better management. To explore the predictive effect of systemic immune-inflammation index (SII) combined with neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), eosinophil (EOS%), and CD4/CD8 on DILI occurrence in TB patients with HBsAg positive. This is a retrospective study enrolling patients who were treated with anti-tuberculosis drugs and infected with hepatitis B virus (HBV) in the Guangzhou Chest Hospital from 2018 to 2023. Population demographics and clinical data of 2643 patients were collected by reviewing electronic medical records. Using a propensity score matching model, the study ultimately included 516 patients (258 patients with DILI and 258 patients without DILI). Logistic regression analysis was conducted to investigate the predictive role of systemic immune-inflammatory biomarkers (SII, NLR, MLR, EOS%, and CD4/CD8) in DILI in hepatitis B virus surface antigen-positive TB patients (HBV-TB-DILI). As compared to patients without DILI, patients with DILI have elevated levels of systemic immune-inflammatory biomarkers (SII, NLR, MLR, EOS%, and CD4/CD8), (all P < .05). The SII, NLR, MLR, PLR, EOS%, and CD4/CD8 are risk factors of HBV-TB-DILI. The NLR, MLR, SII, and EOS% were positively correlated with liver function (P < .001). The combination of SII, NLR, MLR, EOS%, and CD4/CD8 demonstrated good predictive performance for DILI occurrence in HBV-TB patients. The combination of SII, NLR, MLR, EOS%, and CD4/CD8 demonstrated good predictive performance for DILI occurrence in HBV-TB patients.

Saliva-based point-of-care assay to measure the concentration of pyrazinamide using a mobile UV spectrophotometer.

Pyrazinamide, one of the first-line antituberculosis drugs, displays variability in drug exposure that is associated with treatment response. A simple, low-cost assay may be helpful to optimize treatment. This study aimed to develop and validate a point-of-care assay to quantify the concentration of pyrazinamide in saliva. All measurements were conducted using the nano-volume drop function on the mobile ultraviolet (UV) spectrophotometer (NP80, Implen, Germany). Assay development involved applying second derivative spectroscopy in combination with the Savitzky-Golay filter between wavelengths of 200-300 nm to increase spectral resolution. Assay validation included assessing selectivity, linearity, accuracy, precision, carry-over and matrix effects. Specificity was also analysed by evaluating the impact of co-administered medications on pyrazinamide results. Sample stability was measured at various temperatures up to 40°C. The calibration curve (7.5-200 mg/L) was linear (R2 = 0.9991). The overall accuracy (bias%) and precision (CV%) ranged from -0.66% to 5.15%, and 0.56% to 4.95%, respectively. Carry-over and matrix effects were both acceptable with a bias% of <±4% and CV% of <7.5%. Commonly co-administered medications displayed negligible interferences. Levofloxacin displayed analytical interference (bias% = -10.21%) at pyrazinamide concentrations < 25 mg/L, but this will have little clinical implications. Pyrazinamide was considered stable in saliva after 7 days in all storage conditions with a CV% of <6.5% and bias% of <±10.5% for both low- and high-quality control concentrations. A saliva-based assay for pyrazinamide has been successfully developed and validated using the mobile UV spectrophotometer.

Exploring Novel Benzopyran Derivatives as Antitubercular Agents

Background: Tuberculosis (TB) remains a significant global health concern, necessitating the exploration of novel therapeutic agents. Reported antitubercular activities of previously synthesized benzopyran and other oxygen-containing heterocycles motivate us to synthesize and evaluate the antitubercular potential of benzopyran derivatives. Objective: The aim of this study was to combine two scaffolds; one is coumarin (benzopyran-2-one), and another one is piperazine, as both are found in anti-tubercular derivatives. Methods: Through a four-step synthetic approach, compounds SM1-SM10 were synthesized. These derivatives were subsequently evaluated for their in vitro anti-tubercular potential using the resazurin microtiter assay (REMA), with isoniazid as the standard (MIC 0.25 to 0.5μg/mL). Results: Among the synthesized compounds, SM2 and SM8 demonstrated remarkable antitubercular activity, with MICs of 4 and 6μg/mL, respectively. Notably, these MIC values are considerable for the further development of benzopyran derivatives as potent antitubercular agents. Conclusion: Outcomes underscore the potential of benzopyran derivati ves as valuable assets in TB drug discovery, warranting further exploration and development.

Innovative Thiophene Schiff Bases: Synthesis and Evaluation as Antitubercular Agents

Innovative Thiophene Schiff Bases: Synthesis and Evaluation as Antitubercular Agents

Identification of Urinary Glucose and Urinary Ketones in Pulmonary Tuberculosis Patients Receiving Anti-Tuberculosis Drug Therapy (OAT) at the Tlogosari Wetan Health Center

Tuberculosis is a contagious infection caused by Mycobacterium tuberculosis. Anti-Tuberculosis Drug Therapy (OAT) given also has side effects, one of which is hepatotoxicity. Laboratory examination of urine glucose identification can show if there is damage to the kidney glomerulus in the filtration process. OAT such as isoniazid can affect the breakdown of fat and cause increased ketone production, especially in individuals who have low carbohydrate intake so that if the excess amount will be excreted through urine (ketonuria). The purpose of this study was to identify urine glucose and urinary ketones in non-DM pulmonary TB patients with OAT treatment at the Tlogosari Wetan Health Center based on treatment phase, gender, and age. This type of research is descriptive observational with a cross sectional approach. The study sample was a urine sample from a non-DM pulmonary TB patient. The examination method used is dyeing using a reagent strip test. The results of the study from a total of 30 non-DM pulmonary TB patients with OAT therapy (100%). A total of 6 (20%) patients identified urinary glucose, with details of intensive phase treatment 2 (7%) trace urine glucose patients (±), while in advanced phase 2 (7%) patients identified trace urine glucose (±) and 2 (7%) low urine glucose patients (+1). The majority of positive urine glucose results were experienced by men with vulnerable elderly age (46-65 years) as many as 4 patients (14%). The results of urine ketone identification showed that 2 (6.6%) patients were identified with urine ketones, namely trace (±) in the intensive phase treatment, while 15 patients in the advanced phase of urine ketones were all negative.The majority of positive urinary ketone results were experienced by vulnerable men of adult age (26-45 years) as much as 2 caseins (14%). Conclusion: Of the 30 non-DM pulmonary TB patients with OAT therapy who met the inclusion criteria, there were 6 (20%) patients identified with urinary glucose and 2 (6.6%) patients identified with urinary ketones. The impact of this study is expected to encourage non-DM pulmonary TB patients to take OAT and do regular medical check-ups.

Role of Nutraceuticals in Treating Erectile Dysfunction via Inhibition of Phosphodiesterase-5 Enzyme: A Mini Review.

Erectile Dysfunction (ED) is a prevalent sexual health condition affecting a significant portion of the male population worldwide. The conventional therapeutic approaches for ED often involve the use of pharmaceutical agents targeting the phosphodiesterase-5 (PDE5) enzyme. Currently, treatment with PDE-5 inhibitors is the standard approach for ED, and four PDE-5 inhibitors, namely sildenafil, vardenafil, tadalafil, and avanafil, are in use. However, these pharmaceutical interventions may be associated with adverse effects and limitations. As a result, there has been a growing interest in exploring alternative and complementary treatment options for ED, such as nutraceuticals, which are bioactive compounds derived from natural sources. Nutraceuticals, which include vitamins, minerals, herbs, and other dietary supplements, have gained popularity for their potential health benefits. Certain nutraceuticals have demonstrated the ability to modulate various physiological pathways, including those involved in erectile function. A notable mechanism of action is the inhibition of the PDE5 enzyme, which plays a pivotal role in the regulation of cGMP levels. By inhibiting PDE5, nutraceuticals can promote the accumulation of cGMP, leading to enhanced penile blood flow and improved erectile function. A comprehensive analysis of the literature showcases various nutraceutical agents, including plant-derived compounds like flavonoids, polyphenols, and amino acids which have exhibited PDE5 inhibitory effects. Mechanistic insights into their action involve modulation of NO release, cGMP elevation, and relaxation of penile smooth muscles, all critical factors for achieving and sustaining erections. This review focuses on elucidating the role of nutraceuticals in treating erectile dysfunction through the inhibition of the PDE5 enzyme.

Recent Advancements in Benzothiazinones (BTZ) Analogs as DprE1 Inhibitor for Potent Antitubercular Therapeutics

AbstractBenzothiazinone analogs have emerged as a promising class of compounds having potent antimycobacterial activity, particularly against Mycobacterium tuberculosis, the pathogen responsible for tuberculosis. This review highlights the development of benzothiazinone analogs as potential antitubercular agents from the beginning to the recent advancement in the past decade. These compounds have shown potent activity, including drug‐resistant strains of Mycobacterium tuberculosis. Structure–activity relationship studies and modifications have improved their efficacy. Benzothiazinone analogs have favorable pharmacokinetic profiles and show promise in preclinical studies. Challenges include addressing resistance mechanisms and ensuring safety. Their unique mode of action and promising properties make them attractive candidates for the battle against drug‐resistant tuberculosis.

Identification of novel DNA Gyrase inhibitor by combined Pharmacophore modeling, QSAR analysis, Molecular docking, Molecular dynamics, ADMET and DFT approaches

DNA gyrase, an ATP-dependent enzyme, plays a critical role in DNA replication, transcription, and recombination in Mycobacterium tuberculosis (MTB). While fluoroquinolones are effective antibacterial agents targeting DNA gyrase, their clinical use is often limited due to side effects and the emergence of bacterial resistance. In this study, we developed a quantitative structure-activity relationship (QSAR) model to predict the anti-tubercular activity of Quinoline-Aminopiperidine derivatives targeting the DNA gyrase enzyme, using a dataset of 48 compounds obtained from the literature. The QSAR model was validated using both internal and external validation metrics. Model 4, the best predictive model, demonstrated a strong fit with an R² of 0.8393, an adjusted R² (R²adj) of 0.8010, and a lack of fit (LOF) parameter of 0.0626. The QSAR results revealed that DNA gyrase inhibition is significantly influenced by factors such as partition coefficient, molecular flexibility, hydrogen bonding potential, and the presence of fluorine atoms. Twelve quinoline-aminopiperidine derivatives were designed, and their anti-tubercular activity was predicted using QSAR model-4. These compounds were further assessed for pharmacokinetic properties, toxicity, and binding affinity to DNA gyrase. Pharmacophore modeling was also performed and validated using MOE software. The final pharmacophore model includes the features of two aromatic hydrophobic features, one hydrogen bond acceptor, and one hydrogen bond donor. The results indicated that designed compounds QA-3 and dataset compounds C-34 exhibit favorable drug-likeness properties. Molecular dynamics simulations confirmed the stable binding of compounds QA-3 and C-34 to the DNA gyrase protein, highlighting their potential as promising anti-tubercular agents. The developed QSAR Model-4 will facilitate the prediction of anti-tubercular activity in Quinoline-Aminopiperidine derivatives.

Ionic liquid promoted facile one-pot synthesis of phenothiazine-thiazolidin-4-ones as potent antitubercular agents via mycobacterial ATP synthase inhibition

The mycobacterial ATP synthase is responsible for the optimal growth, metabolism and viability of mycobacteria, establishing it as a validated target for the development of anti-TB therapeutics. Herein, we report the facile and efficient one-pot three component synthesis of 2-(10H-phenothiazin-3-yl)-3-substituted thiazolidin-4-one derivatives by using ionic liquid, 1-butyl-3-methylimidazolium bromide [Bmim]Br and their inhibitory potency against mycobacterium tuberculosis H37Rv strain (ATCC-27294). Compound T27 exhibited the highest inhibition activity with an MIC of 0.78 μg/mL, which is twofold and fourfold superior (in terms of the MIC values) to the standard first-line TB drugs isoniazid (MIC: 1.56 μg/mL) and pyrazinamide (MIC: 3.12 μg/mL) respectively. Two other compounds (T25 and T30) are equipotent as the isoniazid. The SAR studies revealed that insertion of 1,2,3-traizole and thiozolidine-2-one rings enhance the anti-TB activity in most of the tested compounds. Also, compound T27 was screened for mycobacterial ATP synthase inhibition activity and it exhibited an IC50 of 0.735 µM in M. smegmatis IMVs. Further, toxicity evaluation against VERO cell lines confirmed null cytotoxicity (selectivity index > 70) of the potent analogues. The title compounds are highly specific towards to the M. tb strain, i.e., most of the compounds exhibited moderate inhibitory potency against the tested bacterial strains (MIC ≥ 6.25 μg/mL). In addition, molecular docking was employed against the active site of the ATP synthase enzyme to validate the binding mechanism and in vitro activity profile of the phenothiazine derivatives. Furthermore, in silico ADME and pharmacokinetic parameters’ prediction indicated good oral bioavailability.

Polyketide Synthase 13 (Pks13) Inhibition: A Potential Target for New Class of Anti-tubercular Agents.

Tuberculosis is one of the deadly infectious diseases that has resurfaced in multiple/ extensively resistant variants (MDR/XDR), threatening humankind. Today's world has a higher prevalence of tuberculosis (TB) than it has ever had throughout human history. Due to severe adverse effects, the marketed medications are not entirely effective in these forms. So, developing new drugs with a promising target is an immense necessity. Pks13 has emerged as a promising target for the mycobacterium. The concluding step of mycolic acid production involved Pks13, a crucial enzyme that helps form the precursor of mycolic acid via the Claisen-condensation reaction. It has five domains at the active site for targeting the enzyme and is used to test chemical entities for their antitubercular activity. Benzofurans, thiophenes, coumestans, N-phenyl indoles, and β lactones are the ligands that inhibit the Pks13 enzyme, showing potential antitubercular properties.

The CRISPR-dCas9 interference system suppresses inhA gene expression in Mycobacterium smegmatis

CRISPR-dead Cas9 interference (CRISPRi) has become a valuable tool for precise gene regulation. In this study, CRISPRi was designed to target the inhA gene of Mycobacterium smegmatis (Msm), a gene necessary for mycolic acid synthesis. Our findings revealed that sgRNA2 induced with 100 ng/ml aTc achieved over 90% downregulation of inhA gene expression and inhibited bacterial viability by approximately 1,000-fold. Furthermore, CRISPRi enhanced the susceptibility of M. smegmatis to isoniazid and rifampicin, which are both 50% and 90% lower than those of the wild-type strain or other strains, respectively. This study highlights the ability of CRISPRi to silence the inhA gene, which impacts bacterial viability and drug susceptibility. The findings provide valuable insights into the utility of CRISPRi as an alternative tool for gene regulation. CRISPRi might be further assessed for its synergistic effect with current anti-tuberculosis drugs and its possible implications for combating mycobacterial infections, especially drug-resistant tuberculosis.

Design, Synthesis and Biological Evaluation of Pyridyltriazole Derivatives as Potent Antitubercular Agents

In current investigation, a new series of pyridyltriazole derivatives were synthesized by conventional methods and characterized through spectroscopic techniques such as IR, NMR (1H) and mass spectroscopy. Based on colour observation and percentage of inhibition, all 24 pyridyltriazole derivatives were subjected to in vitro anti-mycobacterial testing using MABA techniques against the Mycobacterium tuberculosis (H37Rv) strain. It was found that all of the synthesized compounds were efficient in suppressing the M. tuberculosis H37Rv strain at concentrations of 1, 5 and 10 µg/mL. Among all the synthesized compounds, only 2, 3, 6, 7, 8, 11, 14, 15, 18, 20, 21, 22, 23, 24 has good anti-TB efficacy in contrast to the standard medication. According to the in silico ADME prediction, every synthesized molecule has drug-like qualities and is appropriate for oral bioavailability. Furthermore, research utilizing molecular docking have been conducted to get mechanistic understanding and molecular interactions in opposition to the mycobacterial InhA enzyme. Utilizing a molecular docking analysis, hits against specific molecular targets were found. This in silico study delved into the molecular interactions between potential compounds and the Mtbenoyl-reductaseInhA (PDB 5JFO).

Synthesis of Pyridines/Dihydropyridines via Hantzsch Reaction, Structure-activity Relationship and Interactions with Targets: A Review

Pyridines/Dihydropyridines is a basic 6-membered organic aza-heterocyclic compound that has garnered the attention of many researchers in recent times. These molecules have been reported with a diverse range of pharmacological activities like anti-coagulant, antileishmanial and anti-trypanosomal, antitubercular agents, anti-microbial, antioxidant, HIV-1 protease inhibitors, anti-cancer, cardiovascular disease, etc. This review article focuses on different protocols for the Hantzsch reaction using acid catalysts, metal catalysts, and no catalysts for the synthesis of pyridine derivatives. The structure-activity relationship in relation to other biological activities of various pyridine-containing drugs and their interaction with different targets (receptors) has also been highlighted to provide a good understanding to researchers for future research on pyridines.