Synthesis of novel heterocyclic Quinolone compound for anti -tubercular activity

In last few decades, though significant progress has been made in the treatment and control strategies of tubercular infections by introducing new diagnostic and monitoring tools and combination therapy, it still continues to be severe problem. The need of study was only because of there are many drugs in market to treat infection but most of the drugs are showing resistance because of the same it is difficult to treat the infection. In this study we chosen quinolone nucleus for study and over it. Thus with the aim of developing novel molecule with improved potency for treating Mycobacterium tuberculosis H37Rv strain infections and with decreased probability of developing drug resistance. Methodology: The synthesis of Quinolone derivatives, starting from substituted aniline and ethyl acetoacetate, by conventional organic reaction and results of investigations of their anti-mycobacterial activity. Results: MICs of the synthesized compounds are compared with existing drugs Cytotoxicity. The substituted quinolones are synthesized by taking mixture of 7-substituted-2-(3-chloro-2-oxopropyl) quinolin-4(1H)-one and different secondary amines. Many compounds have shown promising activity while some were inactive. Conclusion: It was found that Compound A1, A3, B1, B3, have shown promising anti tubercular activity whereas compound A2, A4, B2, B4 were showing moderate anti tubercular activity against std. Streptomycin

IN SILICO DESIGN OF POTENTIAL 1, 5-BENZOTHIAZEPINE DERIVATIVES AS AN ANTI - CONVULSANT AGENT BY MOLECULAR DOCKING STUDIES

Epilepsy is characterized by the presence of recurrent seizures. A seizure can be defined as “an episodic disturbance of movement, feeling, or consciousness caused by sudden synchronous, inappropriate, and excessive electrical discharges in the cerebral cortex”. One in every three patients with epilepsy is probable to be severely disabled. It is continuing this scenario as an attempt to develop potent and nontoxic anti-convulsant agents. Recently the discovery of benzothiazepine derivatives as an anticonvulsant agent is a significant area for research in medicinal chemistry as it is free from all side effects which is shown by a developed as an anticonvulsant agent. In this paper, we have presented results of 2D, and 3D docking poses studies of a series of 300 (Three series) molecules containing 1,5-benzothiazepine pharmacophore as anti-convulsant agents. Docking analysis was utilized to predict the mechanism of action of the designed derivatives for anticonvulsant potential. All the molecules exhibited a binding score in the range of -82.61 to - 118.25 kcal/mol. Most active molecules from Series 1, 2 and 3 exhibited hydrogen bond interactions with LEU282B, LEU282B and LEU282B. Also for the selected standard sodium phenytoin showed the hydrogen bond interaction with LYS637A. It was noted that the docking score of 1a to 10a, 101b to 110b and 201c to 210c was almost the same as that of selected standard sodium phenytoin. The protein showed hydrogen bonding with all synthesized compound showed potential against epilepsy with GABA nergic mechanism.  Keywords: Anti-convulsant; 1,5-benzothiazepine; V-Life MDS 4.3

SUBLINGUAL VITAMIN D3 DRUG THERAPY IN VITAMIN D DEFICIENCY PATIENTS AT PRAVARA RURAL HOSPITAL

The present study was aimed to study the effect of Sublingual Vitamin D3 on Serum Vitamin D level in Vitamin D deficiency patients. This was a cross-sectional and interventional study. All the Vitamin D deficiency patients of age 18-60years and either gender, willing to participate in the study were included. Patients who had greater than 20 ng/ml were excluded from the study. The total number of participants in our study was 200, out of these 111 males and 89 females, the mean age in our study was 51.07 ± 7.39Yrs. All volunteers were given sublingual vitamin D3 (60,000IU) in six doses every fifteen days of follow up for 3 months. The subject’s serum 25(OH)D levels were estimated before and after the treatment of sublingual vitamin D3. There was a statistically significant difference in serum vitamin D3 level before 16.61±6.71 ng/ml and after 35.80±7.80 ng/ml after treatment with Sublingual Vitamin D3. Six doses of 60,000IU of Vitamin D3 sublingual route having improved the role of serum 25(OH)D levels in the treatment of Vitamin D3 deficiency patients.Keywords: Vitamin D3; Sublingual rout

SYNTHESIS OF COUMARIN HETEROCYCLIC DERIVATIVES WITH IN-VITRO ANTITUBERCULER ACTIVITY

In last few decades, though significant progress has been made in the treatment and control strategies of tubercular infections by introducing new diagnostic and monitoring tools and combination therapy, it still continues to be severe problem. The need of study was only because of there are many drugs in market to treat infection but most of the drugs are showing resistance because of the same it is difficult to treat the infection. In this study we chosen coumarin nucleus for study. Thus with the aim of developing novel molecule with improved potency for treating Mycobacterium tuberculosis H37Rv strain infections and with decreased probability of developing drug resistance. The synthesis of coumarin derivatives, starting from salicyaldehyde and ethyl acetoacetate, by conventional organic reaction and results of investigations of their anti-mycobacterial activity. MICs of the synthesized compounds are compared with existing drugs Cytotoxicity. Many compounds have shown promising activity while some were inactive. It was found that Compound A1, A2, B1, B2, C1, C2 have shown promising antitubercular activity against std. Streptomycin  Keywords: Coumarin derivative, well diffusion method, antitubercular activity

SUBLINGUAL VITAMIN D3 DRUG THERAPY IN VITAMIN D DEFICIENCY PATIENTS AT PRAVARA RURAL HOSPITAL

The present study was aimed to study the effect of Sublingual Vitamin D3 on Serum Vitamin D level in Vitamin D deficiency patients. This was a cross-sectional and interventional study. All the Vitamin D deficiency patients of age 18-60years and either gender, willing to participate in the study were included. Patients who had greater than 20 ng/ml were excluded from the study. The total number of participants in our study was 200, out of these 111 males and 89 females, the mean age in our study was 51.07 ± 7.39Yrs. All volunteers were given sublingual vitamin D3 (60,000IU) in six doses every fifteen days of follow up for 3 months. The subject’s serum 25(OH)D levels were estimated before and after the treatment of sublingual vitamin D3. There was a statistically significant difference in serum vitamin D3 level before 16.61±6.71 ng/ml and after 35.80±7.80 ng/ml after treatment with Sublingual Vitamin D3. Six doses of 60,000IU of Vitamin D3 sublingual route having improved the role of serum 25(OH)D levels in the treatment of Vitamin D3 deficiency patients.Keywords: Vitamin D3; Sublingual rout

IN SILICO DESIGN OF POTENTIAL 1, 5-BENZOTHIAZEPINE DERIVATIVES AS AN ANTI - CONVULSANT AGENT BY MOLECULAR DOCKING STUDIES

Epilepsy is characterized by the presence of recurrent seizures. A seizure can be defined as “an episodic disturbance of movement, feeling, or consciousness caused by sudden synchronous, inappropriate, and excessive electrical discharges in the cerebral cortex”. One in every three patients with epilepsy is probable to be severely disabled. It is continuing this scenario as an attempt to develop potent and nontoxic anti-convulsant agents. Recently the discovery of benzothiazepine derivatives as an anticonvulsant agent is a significant area for research in medicinal chemistry as it is free from all side effects which is shown by a developed as an anticonvulsant agent. In this paper, we have presented results of 2D, and 3D docking poses studies of a series of 300 (Three series) molecules containing 1,5-benzothiazepine pharmacophore as anti-convulsant agents. Docking analysis was utilized to predict the mechanism of action of the designed derivatives for anticonvulsant potential. All the molecules exhibited a binding score in the range of -82.61 to - 118.25 kcal/mol. Most active molecules from Series 1, 2 and 3 exhibited hydrogen bond interactions with LEU282B, LEU282B and LEU282B. Also for the selected standard sodium phenytoin showed the hydrogen bond interaction with LYS637A. It was noted that the docking score of 1a to 10a, 101b to 110b and 201c to 210c was almost the same as that of selected standard sodium phenytoin. The protein showed hydrogen bonding with all synthesized compound showed potential against epilepsy with GABA nergic mechanism.  Keywords: Anti-convulsant; 1,5-benzothiazepine; V-Life MDS 4.3

Eruptions in focus: cefadroxil and the uncommon realm of fixed-drug reactions: a case report

This case report explores a rare case of localized fixed-drug eruption (FDE) induced by cefadroxil, a first-generation cephalosporin. FDE, characterized by recurrent lichenoid lesions at specific sites upon drug exposure, is an immunological cutaneous adverse reaction. The incidence of FDE due to cephalosporins is infrequently reported, making this case noteworthy. We present a 51-year-old male who developed brownish-black patches and painful blisters on his extremities after initiating treatment with Cefadroxil for a minor toe injury. The patient's symptoms, clinical course, and subsequent recovery are detailed. Treatment involved corticosteroids, antibiotics, and topical agents. The report also provides immunological insights into FDE pathogenesis, involving CD8+ memory T cells, cytokine production, and the role of CD4+ regulatory T cells. While the exact pathogenesis of FDE remains elusive, this report sheds light on the mechanisms contributing to the self-limited nature of these eruptions. Causality assessment using the Naranjo algorithm categorized the association between cefadroxil and FDE as probable. This case report contributes to the limited literature on FDE caused by cephalosporins and underscores the importance of recognizing and managing such dermatological reactions. The broader implications of understanding FDE pathogenesis and the rarity of cephalosporin-induced cases provides valuable insights for clinicians and researchers